Thermal pain

Bristol-Myers Squibb has recently disclosed two different series of carbamate-based FAAH inhibitors. The first of these is a series of 4,5-diaryl-imidazoles in which 30 compounds are specifically claimed, an example being compound (57). This compound is reported to have an IC50 value of < 10 nM. In addition, (57) was also active in vivo in rodent models of chemo-induced, thermal and neuropathic pain [72]. The second series of compounds is based on oxime carbamoyl FAAH inhibitors such as (58). Compound (58) is reported to have an IC50 value of < 10 nM and activity in rodent models of inflammatory pain, thermal pain and inflammatory oedema [73]. 

A model of thermal pain. Mice or rats are placed on a heated metal plate of variable temperature. Depending on the temperature (48-58 °C), a weak or strong pain stimulus is induced. Animals respond either by licking their paws or by jumping. Analgesics increase the latency for this pain reaction. The low temperature hot plate detects a broader spectrum of less efficacious analgesics in comparison to its high temperature modification or the tail flick test (Eddy and Leimbach J. Pharmacol. 1953, 107, 385). 

Yosipovitch, G., Szolar, C., Hui, X., and Maibach, H.I., Effect of topically applied menthol on thermal, pain and itch sensation and biophysical properties of the skin, Arch. Dermatol. Res., 288, 245-248, 1996. 

NRM, or amygdala generates antinociception in the acute pain test (Reny-Palasse et al 1989 Webster et al., 1983). ICV administration of TRH has induced analgesic effect with similar or higher potency than morphine in mechanical but not thermal pain tests (Boschi et al., 1983). Its antinociceptive effects are mediated via activation of both descending monoaminergic and serotoninergic pathways (Tanabe et al,... 

NAGly has been intensively studied (see Section 6.1.3), but only one report has investigated the antinociceptive potency of NAGABA and NAAla. It has been found that their IT administration does not produce an increase in mechanical and thermal pain threshold in the inflammatory pain model (Succar et al.,... 

Abbott FV, Franklin KB, Libman RB. 1986. A dose-ratio comparison of Mu and Kappa agonists in formalin and thermal pain. Life Sci 39 2017-2024. 

Clark WC, Janal MN, Zeidenberg P, Nahas GG (1981) Effects of moderate and high doses of marihuana on thermal pain a sensory decision theory analysis. J Clin Pharmacol 21 299S-310S... 

Hot-plate test The test animal is put on a heated surface ( a hot plate ) and the thermal pain reflexes are recorded. 

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