The hot plate test is a test of the pain response in animals, similar to the

tail flick test The tail flick test is a test of the pain response in animals, similar to the hot plate test. It is used in basic pain research and to measure the effectiveness of analgesics, by observing the reaction to heat. It was first described by D'Amour ...

. Both hot plate and tail-flick methods are used generally for centrally acting analgesic, while peripherally acting drugs are ineffective in these tests but sensitive to acetic acid-induced writhing test. The hot plate test is used in basic

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, ...

research and in

testing An examination (exam or evaluation) or test is an educational assessment intended to measure a test-taker's knowledge, skill, aptitude, physical fitness, or classification in many other topics (e.g., beliefs). A test may be administered verba ...

the effectiveness of

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

s by observing the reaction to pain caused by heat. It was proposed by Eddy and Leimbach in 1953. They used a behavioral model of

nociception Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, co ...

where behaviors such as jumping and hind paw-licking are elicited following a noxious thermal stimulus. Licking is a rapid response to painful thermal stimuli that is a direct indicator of nociceptive threshold. Jumping represents a more elaborated response, with a latency, and encompasses an emotional component of escaping.

Procedure

* A transparent glass cylinder is used to keep the animal on the heated surface of the plate. * The temperature of the hot plate is set using a thermoregulated water-circulated pump. * The time of latency is defined as the time period between the zero point, when the animal is placed on the hot plate surface, and the time when the animal licks its paw or jumps off to avoid thermal pain.

Research findings

Sex studies using antidepressants

Significant differences in pain sensitivity in male and female mice have been observed in laboratory studies. The

SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

paroxetine Paroxetine, sold under the brand names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder ...

did not display a gender difference in antinociceptive effects in mice.

Ion channels

Voltage-gated ion channels are implicated in pain sensation and transmission signaling mechanisms within both

peripheral A peripheral or peripheral device is an auxiliary device used to put information into and get information out of a computer. The term ''peripheral device'' refers to all hardware components that are attached to a computer and are controlled by the ...

nociceptors and the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...

. Specific ion channel isoforms such as Nav1.7 and Nav1.8

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 ...

s and Cav3.2 T-type

calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables e ...

s have distinct pro-nociceptive roles.

Opioid receptors

Activation of the

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical � ...

(MOR) and norepinephrine reuptake inhibition (NRI) are mechanisms of acute and chronic pain. OPRM1 knockout mice were used to determine the relative contribution of MOR activation to

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 ...

and

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 ...

induced analgesia. Wild-type mice exhibited an antinociceptive effect ten times that of OPM1 knockouts. However, the OPRM1 knockouts still exhibited a slight analgesic effect to tapentadol but not to morphine. This indicated that the antinociceptive effect of tapentadol is based on a combined mechanism of action involving both MOR and NRI.

Benzodiazepines and GABA receptors

Diazepam Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, a ...

is a

GABAA receptor The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon opening, the GABAA receptor on ...

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...

that is an anxiety modulator. Studies using diazepam with the hot plate test showed that diazepam modified the behavioral structure of the pain response not from pain modulation but rather by reducing anxiety levels.

Ethics

The Ethical Committee of the International Association for the Study of Pain has developed guidelines for the ethical use of this procedure. In the United States, such experiments must be approved by an

Institutional Animal Care and Use Committee Institutional Animal Care and Use Committees (IACUCs) are centrally important in applying laws about animal research in the United States. Similar systems operate in other countries, but generally under different titles; for example, in Canada a t ...

.Institutional Animal Care and Use Committee
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References

{{pain Pain scales Animal testing techniques Laboratory techniques