Capsaicin-induced Allodynia Research Articles

Effect of Oral Mexiletine on Capsaicin-Induced Allodynia and Hyperalgesia

Effect of Oral Mexiletine on Capsaicin-Induced Allodynia and Hyperalgesia

Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia

Clonidine is approved in the US for epidural administration in the treatment of intractable neuropathic cancer pain, but is also administered intrathecally for this indication and both epidurally and intrathecally in the treatment of acute, postoperative pain. The purpose of the current study was to estimate the relative potency of clonidine by epidural and intrathecal routes in the treatment of capsaicin-induced hyperalgesia and allodynia as a model of central hypersensitivity and of noxious heat as a model of acute pain. Twenty-four healthy volunteers were randomized to receive either intrathecal clonidine (75, 150, or 300 μg) or epidural clonidine (150, 300, or 600 μg) and rated pain from a Peltier-controlled thermode at a lumbar, thoracic, and cervical dermatomal site before and after drug administration. In addition, they rated pain from intradermal capsaicin injections at a lumbar dermatome before and 60 min after clonidine injection and described areas of hyperalgesia and allodynia to mechanical stimuli. Clonidine's effect differed with route of administration and modality of sensory testing. For acute thermal pain, intrathecal clonidine produced a dose-dependent analgesia with a lumbar>thoracic>cervical gradient, whereas only one dose of epidural clonidine reduced thermal pain and this was at the thoracic testing site. In contrast, the potency of clonidine to reduce capsaicin-induced allodynia was similar between the two routes of injection, and, for hyperalgesia, clonidine was only slightly more potent after intrathecal than epidural injection. These data support clinical studies from non-comparative trials and suggest there is a >6-fold potency ratio of intrathecal: epidural administration of clonidine for acute pain, but a <2-fold potency ratio for these routes for mechanical hypersensitivity.

Local administration of delta9-tetrahydrocannabinol attenuates capsaicin-induced thermal nociception in rhesus monkeys: a peripheral cannabinoid action.

Cannabinoids can reduce nociceptive responses by acting on peripheral cannabinoid receptors in rodents. The study was conducted to evaluate the hypothesis that local administration of delta9-tetrahydrocannabinol (delta9-THC) can attenuate capsaicin-induced nociception in rhesus monkeys. Capsaicin (100 microg) was applied locally in the tail of rhesus monkeys to evoke a nociceptive response, thermal allodynia, in normally innocuous 46 degrees C water. delta9-THC (10-320 microg) was coadministered with capsaicin in the tail to assess local antinociceptive effects. In addition, a local antagonism study was performed to confirm the selectivity of delta9-THC action. delta9-THC dose-dependently inhibited capsaicin-induced allodynia. This local antinociception was antagonized by small doses (10-100 microg) of the cannabinoid CB1 antagonist, SR141716A, applied in the tail. However, 100 microg SR141716A injected subcutaneously in the back did not antagonize local delta9-THC. These results indicate that the site of action of locally applied delta9-THC is in the tail. It provides functional evidence that activation of peripheral cannabinoid CB1 receptors can attenuate capsaicin-induced thermal nociception in non-human primates and suggests a new approach for cannabinoids in pain management.

Attenuation of experimental pruritus and mechanically evoked dysesthesiae in an area of cutaneous allodynia

We investigated the effects of tactile allodynia on the itch and mechanically evoked dysesthesiae produced by an intradermal injection of histamine in human volunteers. After an intradermal injection of capsaicin into the volar surface of one forearm, there developed an area of tactile allodynia to stroking and hyperalgesia to pricking the skin. Histamine was then injected simultaneously into the area of allodynia (experimental arm) and into the opposite forearm (control arm). Magnitude estimates of itch were obtained every 15 s for 5 min, and the areas of cutaneous hyperalgesia (pricking-evoked pain), alloknesis (stroking-evoked itch), hyperknesis (pricking-evoked itch) and wheal and flare were measured. The areas of wheal and flare were not significantly different on the two arms. The magnitude of itch and the areas of hyperknesis and alloknesis developed normally on the control arm but were absent or greatly reduced on the experimental arm. Thus, both the itch and the alloknesis and hyperknesis normally induced by histamine were absent or greatly reduced when histamine was injected in an area of capsaicin-induced allodynia. These results are compatible with the hypothesis that activity in capsaicin-sensitive, nociceptive primary afferent neurons evokes a central neuronal inhibitory process that prevents or reduces the itch and mechanically evoked dysesthesiae normally produced by an intradermal injection of histamine.