An analgesic drug, also called simply an analgesic (
American English
American English, sometimes called United States English or U.S. English, is the set of variety (linguistics), varieties of the English language native to the United States. English is the Languages of the United States, most widely spoken lan ...
), analgaesic (
British English
British English (BrE, en-GB, or BE) is, according to Lexico, Oxford Dictionaries, "English language, English as used in Great Britain, as distinct from that used elsewhere". More narrowly, it can refer specifically to the English language in ...
), pain reliever, or painkiller, is any member of the group of
drugs
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalat ...
used to achieve relief from
pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
(that is, analgesia or
pain management
Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals pr ...
). It is typically used to induce cooperation with a medical procedure. Analgesics are conceptually distinct from
anesthetics, which temporarily reduce, and in some instances eliminate,
sensation
Sensation (psychology) refers to the processing of the senses by the sensory system.
Sensation or sensations may also refer to:
In arts and entertainment In literature
*Sensation (fiction), a fiction writing mode
*Sensation novel, a British ...
, although analgesia and
anesthesia
Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...
are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.
Analgesic choice is also determined by the type of pain: For
neuropathic pain
Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...
, traditional analgesics are less effective, and there is often benefit from classes of drugs that are not normally considered analgesics, such as
tricyclic antidepressants
Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
and
anticonvulsant
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
s.
Various analgesics, such as many
NSAIDs, are available
over the counter
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
in most countries, whereas various others are
prescription drug
A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...
s owing to the substantial risks and high chances of
overdose
A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. ,
misuse
Abuse is the improper usage or treatment of a thing, often to unfairly or improperly gain benefit. Abuse can come in many forms, such as: physical or verbal maltreatment, injury, assault, violation, rape, unjust practices, crimes, or other t ...
, and
addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
in the absence of medical supervision.
Etymology
The word ''analgesic'' derives from
Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
''an-'' (, "without"), ''álgos'' (, "pain"), and ''-ikos'' (, forming
adjective
In linguistics, an adjective (list of glossing abbreviations, abbreviated ) is a word that generally grammatical modifier, modifies a noun or noun phrase or describes its referent. Its semantic role is to change information given by the noun.
Tra ...
s). Such drugs were usually known as
anodynes before the 20th century.
Classification
Analgesics are typically classified based on their mechanism of action.
Paracetamol (acetaminophen)
Paracetamol, also known as acetaminophen or APAP, is a medication used to treat
pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
and
fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
.
It is typically used for mild to moderate pain.
In combination with
opioid pain medication, paracetamol is now used for more severe pain such as
cancer pain and after surgery. It is typically used either by mouth or
rectally
The rectum is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the sigmoid colon) at the le ...
but is also available
intravenously
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
.
Effects last between two and four hours.
Paracetamol is classified as a mild analgesic.
Paracetamol is generally safe at recommended doses.
NSAIDs
Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs), are a
drug class
A drug class is a set of medications and other compounds that have a similar chemical structures, the same mechanism of action (i.e. binding to the same biological target), a related mode of action, and/or are used to treat the same disease.
In ...
that groups together
drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
s that decrease pain
and
lower fever, and, in higher doses, decrease
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
.
The most prominent members of this group of drugs,
aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
,
ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...
and
naproxen
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formulati ...
, are all available
over the counter
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
in most countries.
COX-2 inhibitors
These drugs have been derived from NSAIDs. The
cyclooxygenase enzyme inhibited by NSAIDs was discovered to have at least two different versions: COX1 and COX2. Research suggested most of the adverse effects of NSAIDs to be mediated by blocking the COX1 (
constitutive) enzyme, with the analgesic effects being mediated by the COX2 (
inducible
Induction, Inducible or Inductive may refer to:
Biology and medicine
* Labor induction (birth/pregnancy)
* Induction chemotherapy, in medicine
* Induced stem cells, stem cells derived from somatic, reproductive, pluripotent or other cell typ ...
) enzyme. Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). These drugs (such as
rofecoxib
Rofecoxib is a COX-2 inhibitor, COX-2 selective nonsteroidal anti-inflammatory drug (NSAID). It was marketed by Merck & Co. to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenor ...
,
celecoxib, and
etoricoxib
Etoricoxib, sold under the trade name Arcoxia, is a selective COX-2 inhibitor from McOLSON Research Laboratories. Currently it is approved in more than 80 countries worldwide but not in the US, where the Food and Drug Administration (FDA) has r ...
) are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular.
After widespread adoption of the COX-2 inhibitors, it was discovered that most of the drugs in this class increase the risk of
cardiovascular event
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, ...
s by 40% on average. This led to the withdrawal of rofecoxib and valdecoxib, and warnings on others. Etoricoxib seems relatively safe, with the risk of
thrombotic
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...
events similar to that of non-coxib NSAID diclofenac.
Opioids
Morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
, the archetypal
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
, and other opioids (e.g.,
codeine
Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...
,
oxycodone
Oxycodone, sold under various brand names such as Roxicodone and OxyContin (which is the extended release form), is a strong, semi-synthetic opioid used medically for treatment of moderate to severe pain. It is highly addictive and a commonly ...
,
hydrocodone
Hydrocodone, also known as dihydrocodeinone, is an opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe en ...
,
dihydromorphine
Dihydromorphine (Paramorfan, Paramorphan) is a semi-synthetic opioid structurally related to and derived from morphine. The 7,8-double bond in morphine is reduced to a single bond to get dihydromorphine.Rama Rao Nadendla. Principles Of Organic ...
,
pethidine
Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a synthetic opioid analgesic, pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemis ...
) all exert a similar influence on the
cerebral opioid receptor
Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin r ...
system.
Buprenorphine is a
partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...
of the μ-opioid receptor, and
tramadol
Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an h ...
is a serotonin norepinephrine reuptake inhibitor (SNRI) with weak μ-opioid receptor agonist properties.
Tramadol
Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an h ...
is structurally closer to
venlafaxine
Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic di ...
than to
codeine
Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...
and delivers analgesia by not only delivering "opioid-like" effects (through mild agonism of the
mu receptor) but also by acting as a weak but fast-acting
serotonin releasing agent
A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter e ...
and
norepinephrine reuptake inhibitor
A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epineph ...
.
Tapentadol
Tapentadol, brand names Nucynta among others, is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). Analgesia occurs wit ...
, with some structural similarities to tramadol, presents what is believed to be a novel drug working through two (and possibly three) different modes of action in the fashion of both a traditional opioid and as an SNRI. The effects of serotonin and
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
on pain, while not completely understood, have had causal links established and drugs in the SNRI class are commonly used in conjunction with opioids (especially tapentadol and tramadol) with greater success in pain relief.
Dosing of all opioids may be limited by opioid toxicity (confusion, respiratory depression,
myoclonic jerks
Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...
and pinpoint pupils), seizures (
tramadol
Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an h ...
), but opioid-tolerant individuals usually have higher dose ceilings than patients without tolerance.
Opioids, while very effective analgesics, may have some unpleasant side-effects. Patients starting morphine may experience
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
and
vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
(generally relieved by a short course of
antiemetics such as
phenergan
Promethazine is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people ...
).
Pruritus
Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
(itching) may require switching to a different opioid.
Constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
occurs in almost all patients on opioids, and
laxative
Laxatives, purgatives, or aperients are substances that loosen stools and increase bowel movements. They are used to treat and prevent constipation.
Laxatives vary as to how they work and the side effects they may have. Certain stimulant, lubri ...
s (
lactulose
Lactulose is a non-absorbable sugar used in the treatment of constipation and hepatic encephalopathy. It is used by mouth for constipation and either by mouth or in the rectum for hepatic encephalopathy. It generally begins working after 8–12 ...
,
macrogol
Macrogol, also known as polyethylene glycol (PEG), is used as a medication to treat constipation in children and adults. It is also used to empty the bowels before a colonoscopy. It is taken by mouth. Benefits usually occur within three days. ...
-containing or co-danthramer) are typically co-prescribed.
[Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).]
When used appropriately, opioids and other central analgesics are safe and effective; however, risks such as addiction and the body's becoming used to the drug (tolerance) can occur. The effect of tolerance means that frequent use of the drug may result in its diminished effect. When safe to do so, the dosage may need to be increased to maintain effectiveness against tolerance, which may be of particular concern regarding patients with chronic pain and requiring an analgesic over long periods. Opioid tolerance is often addressed with
opioid rotation therapy in which a patient is routinely switched between two or more non-cross-tolerant opioid medications in order to prevent exceeding safe dosages in the attempt to achieve an adequate analgesic effect.
Opioid tolerance should not be confused with
opioid-induced hyperalgesia
Opioid-induced hyperalgesia (OIH) or opioid-induced abnormal pain sensitivity, also called paradoxical hyperalgesia, is generalized pain caused by the long-term use of opioids such as morphine, oxycodone, and methadone. OIH is not necessarily confi ...
. The symptoms of these two conditions can appear very similar but the mechanism of action is different. Opioid-induced hyperalgesia is when exposure to opioids increases the sensation of pain (
hyperalgesia
Hyperalgesia ( or ; 'hyper' from Greek ὑπέρ (huper, “over”), '-algesia' from Greek algos, ἄλγος (pain)) is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and can ...
) and can even make non-painful stimuli painful (
allodynia).
Alcohol
Alcohol has biological, mental, and social effects which influence the consequences of using alcohol for pain.
Moderate use of alcohol can lessen certain types of pain in certain circumstances.
The majority of its analgesic effects come from antagonizing NMDA receptors, similarly to ketamine, thus decreasing the activity of the primary excitatory (signal boosting)
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
, glutamate. It also functions as an analgesic to a lesser degree by increasing the activity of the primary inhibitory (signal reducing) neurotransmitter, GABA.
Attempting to use alcohol to treat pain has also been observed to lead to negative outcomes including excessive drinking and
alcohol use disorder
Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomin ...
.
Cannabis
''Medical cannabis'', or ''medical marijuana'', refers to
cannabis
''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternatively ...
or its
cannabinoids
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...
used to treat disease or improve symptoms. There is evidence suggesting that cannabis can be used to treat
chronic pain and
muscle spasms
A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder.
A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle c ...
, with some trials indicating improved relief of neuropathic pain over opioids.
Combinations
Analgesics are frequently used in combination, such as the
paracetamol
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
and
codeine
Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...
preparations found in many non-prescription pain relievers. They can also be found in combination with vasoconstrictor drugs such as
pseudoephedrine
Pseudoephedrine (PSE) is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent in higher doses.
It was first characteri ...
for
sinus
Sinus may refer to:
Anatomy
* Sinus (anatomy), a sac or cavity in any organ or tissue
** Paranasal sinuses, air cavities in the cranial bones, especially those near the nose, including:
*** Maxillary sinus, is the largest of the paranasal sinuses, ...
-related preparations, or with
antihistamine
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...
drugs for people with allergies.
While the use of paracetamol, aspirin,
ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...
,
naproxen
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formulati ...
, and other
NSAIDS concurrently with weak to mid-range opiates (up to about the hydrocodone level) has been said to show beneficial synergistic effects by combating pain at multiple sites of action,
several combination analgesic products have been shown to have few efficacy benefits when compared to similar doses of their individual components. Moreover, these combination analgesics can often result in significant adverse events, including accidental overdoses, most often due to confusion that arises from the multiple (and often non-acting) components of these combinations.
Alternative medicine
There is some evidence that some treatments using alternative medicine can relieve some types of pain more effectively than
placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
.
[*
*
* ] The available research concludes that more research would be necessary to better understand the use of alternative medicine.
Other drugs
Nefopam
Nefopam, sold under the brand name Acupan among others, is a centrally acting, non-opioid painkilling medication, that is primarily used to treat moderate to severe pain.
Nefopam acts in the brain and spinal cord to relieve pain via novel mecha ...
—a monoamine reuptake inhibitor, and calcium and sodium channel modulator—is also approved for the treatment of moderate to severe pain in some countries.
Flupirtine
Flupirtine is an aminopyridine that functions as a centrally acting non-opioid analgesic that was originally used as an analgesic for acute and chronic pain but in 2013 due to issues with liver toxicity, the European Medicines Agency restricte ...
is a centrally acting K+ channel opener with weak
NMDA antagonist
NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...
properties. It was used in Europe for moderate to strong pain, as well as its
migraine
Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...
-treating and muscle-relaxant properties. It has no significant
anticholinergic properties, and is believed to be devoid of any activity on dopamine, serotonin, or histamine receptors. It is not addictive, and tolerance usually does not develop. However, tolerance may develop in some cases.
Ziconotide
Ziconotide (SNX–111; Prialt), also called intrathecal ziconotide (ITZ) because of its administration route, is an atypical analgesic agent for the amelioration of severe and chronic pain. Derived from ''Conus magus'', a cone snail, it is the ...
, a blocker of potent
N‐type voltage‐gated calcium channels, is administered
intrathecally
Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is useful in spinal anesthesia, chemotherapy, or pain m ...
for the relief of severe, usually cancer-related pain.
Adjuvants
Certain drugs that have been introduced for uses other than analgesics are also used in pain management. Both first-generation (such as
amitriptyline) and newer antidepressants (such as
duloxetine
Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth. It is a serotoni ...
) are used alongside NSAIDs and opioids for pain involving nerve damage and similar problems. Other agents directly potentiate the effects of analgesics, such as using
hydroxyzine
Hydroxyzine, sold under the brand names Atarax, Vistaril and others, is an antihistamine medication. It is used in the treatment of itchiness, insomnia, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or in ...
,
promethazine
Promethazine is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people ...
,
carisoprodol
Carisoprodol, sold under the brand name Soma among others, is a medication used for musculoskeletal pain. Use is only approved for up to three weeks. Effects generally begin within half an hour and last for up to six hours. It is taken orally.
...
, or
tripelennamine
Tripelennamine, sold under the brand name Pyribenzamine by Novartis, is a drug that is used as an antipruritic and first-generation antihistamine. It can be used in the treatment of asthma, hay fever, rhinitis, and urticaria, but is now less co ...
to increase the pain-killing ability of a given dose of opioid analgesic.
Adjuvant analgesics, also called atypical analgesics, include
orphenadrine
Orphenadrine (sold under many brand names) is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Pa ...
,
mexiletine
Mexiletine (INN) (sold under the brand names Mexitil and Namuscla) is a medication used to treat abnormal heart rhythms, chronic pain, and some causes of muscle stiffness. Common side effects include abdominal pain, chest discomfort, drowsiness, ...
,
pregabalin
Pregabalin, sold under the brand name Lyrica among others, is an anticonvulsant, analgesic and anxiolytic medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, opioid withdrawal and generalized anxiety disord ...
,
gabapentin
Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabet ...
,
cyclobenzaprine
Cyclobenzaprine (sold under the brand name Flexeril, among others) is a medication used for muscle spasms from musculoskeletal conditions of sudden onset. It is not useful in cerebral palsy. It is taken by mouth. Use is not recommended for mor ...
,
hyoscine
Scopolamine, also known as hyoscine, or Devil's Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is formally used as a medication for treating motion sickness and postoperative nausea and vomiting ...
(scopolamine), and other drugs possessing anticonvulsant, anticholinergic, and/or antispasmodic properties, as well as many other drugs with CNS actions. These drugs are used along with analgesics to modulate and/or modify the action of opioids when used against pain, especially of neuropathic origin.
Dextromethorphan
Dextromethorphan (DXM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. In 2022, the FDA approved a formulation of it combined with bu ...
has been noted to slow the development of and reverse tolerance to opioids, as well as to exert additional analgesia by acting upon
NMDA
''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...
receptors, as does
ketamine
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...
. Some analgesics such as
methadone
Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...
and
ketobemidone
Ketobemidone, sold under the brand name Ketogan among others, is a powerful synthetic opioid painkiller. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted, in part, by its m ...
and perhaps
piritramide
Piritramide(R-3365, trade names Dipidolor, Piridolan, Pirium and others) is a synthetic opioid analgesic (narcotic painkiller) that is marketed in certain European countries including: Austria, Belgium, Czech Republic, Slovenia, Germany and the ...
have intrinsic NMDA action.
High-alcohol
liquor
Liquor (or a spirit) is an alcoholic drink produced by distillation of grains, fruits, vegetables, or sugar, that have already gone through alcoholic fermentation. Other terms for liquor include: spirit drink, distilled beverage or hard ...
, two forms of which were found in the US Pharmacopoeia up until 1916 and in common use by physicians well into the 1930s, has been used in the past as an agent for dulling pain, due to the
CNS depressant effects of
ethyl alcohol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a hyd ...
, a notable example being the
American Civil War
The American Civil War (April 12, 1861 – May 26, 1865; also known by other names) was a civil war in the United States. It was fought between the Union ("the North") and the Confederacy ("the South"), the latter formed by states th ...
. However, the ability of alcohol to relieve severe pain is likely inferior to many analgesics used today (e.g., morphine, codeine). As such, in general, the idea of alcohol for analgesia is considered a primitive practice in virtually all industrialized countries today.
The
anticonvulsant
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
carbamazepine is used to treat neuropathic pain. Similarly, the
gabapentinoid
Gabapentinoids, also known as α2δ ligands, are a class of drugs that are derivatives of the inhibitory neurotransmitter gamma-Aminobutyric acid (GABA) (i.e., GABA analogues) which block α2δ subunit-containing voltage-dependent calcium chan ...
s
gabapentin
Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabet ...
and
pregabalin
Pregabalin, sold under the brand name Lyrica among others, is an anticonvulsant, analgesic and anxiolytic medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, opioid withdrawal and generalized anxiety disord ...
are prescribed for neuropathic pain, and phenibut is available without prescription. Gabapentinoids work as α2δ-subunit blockers of
voltage-gated calcium channel
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeabi ...
s, and tend to have other mechanisms of action as well. Gabapentinoids are all
anticonvulsant
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
s, which are most commonly used for neuropathic pain, as their mechanism of action tends to inhibit pain sensation originating from the nervous system.
Other uses
Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be treated with an
ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...
- or
diclofenac
Diclofenac, sold under the brand name Voltaren, among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It is taken by mouth or rectally in a suppository, used by injection, or ...
-containing gel (The labeling for topical diclofenac has been updated to warn about drug-induced hepatotoxicity.);
capsaicin
Capsaicin (8-methyl-''N''-vanillyl-6-nonenamide) ( or ) is an active component of chili peppers, which are plants belonging to the genus ''Capsicum''. It is a chemical irritant for mammals, including humans, and produces a sensation of burning ...
also is used
topical
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
ly.
Lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
, an
anesthetic, and
steroids
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
may be injected into joints for longer-term pain relief. Lidocaine is also used for painful
mouth sore
A mouth ulcer (aphtha) is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying cause ...
s and to numb areas for
dental work and minor medical procedures. In February 2007 the FDA notified consumers and healthcare professionals of the potential hazards of topical anesthetics entering the bloodstream when applied in large doses to the skin without medical supervision. These topical anesthetics contain anesthetic drugs such as lidocaine, tetracaine, benzocaine, and prilocaine in a cream, ointment, or gel.
Uses
Topical
nonsteroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
provide pain relief in common conditions such as muscle sprains and overuse injuries. Since the side effects are also lesser, topical preparations could be preferred over oral medications in these conditions.
List of drugs with comparison
Research
Some novel and investigational analgesics include subtype-selective
voltage-gated sodium channel
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
blockers such as
funapide
Funapide (INN) (former developmental code names TV-45070 and XEN402) is a novel analgesic under development by Xenon Pharmaceuticals (formerly in partnership with Teva Pharmaceutical Industries) for the treatment of a variety of chronic pain con ...
and
raxatrigine
Vixotrigine (, ), formerly known as raxatrigine (, ), is an analgesic which is under development by Convergence Pharmaceuticals for the treatment of lumbosacral radiculopathy (sciatica) and trigeminal neuralgia (TGN). Vixotrigine was originally c ...
, as well as multimodal agents such as
ralfinamide
Ralfinamide (INN) (code names NW-1029, FCE-26742A, PNU-0154339E) is a multimodal drug which is under investigation by Newron Pharmaceuticals for the treatment of neuropathic pain and other pain conditions such as post-operative dental pain. ...
.
See also
*
Audioanalgesia
Audioanalgesia (or audio-analgesia) is the relief of pain (analgesia) using white noise or music (that is, via audio equipment) without using pharmacological agents (that is, without analgesic drugs), usually during painful medical procedures such ...
*
Electroanalgesia Electroanalgesia is a form of analgesia, or pain relief, that uses electricity to ease pain. Electrical devices can be internal or external, at the site of pain (local) or delocalized throughout the whole body. It works by interfering with the elec ...
*
Pain management
Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals pr ...
*
Patient-controlled analgesia
Patient-controlled analgesia (PCA) is any method of allowing a person in pain to administer their own pain relief. The infusion is programmable by the prescriber. If it is programmed and functioning as intended, the machine is unlikely to deliver ...
*
Pain in babies
Pain in babies, and whether babies feel pain, has been a large
subject of debate within the medical profession for centuries. Prior to the late nineteenth century it was generally considered that babies hurt more easily than adults. It was only ...
*
Congenital analgesia (insensitivity to pain)
References
Citations
Sources
* .
* .
{{Authority control
Pain
Opioids
Agnosia