Neuropathic pain as a process: reversal of chronification in an animal model

Peripheral neuropathic pain arises from trauma to sensory nerves. Other types of acute neurotrauma such as stroke and spinal cord injury are treated immediately, largely to prevent secondary damage. To pursue the possibility that neuropathic pain may also be amenable to early treatment, a rat model of neuropathic pain was induced using a 2-mm polyethylene cuff implanted around one sciatic nerve. Within 24 hours, hypersensitivity to von Frey hair stimulation appeared, as indicated by decreased paw withdrawal thresholds. When the cuff was removed 24 hours after implantation, readings returned to pre-implantation levels starting as early as day 18. When the cuff was removed after 4 days, there was a period of initial hypersensitivity, and then an increase toward baseline at two time points near the end of the study; therefore, only a partial recovery toward pre-implantation values occurred. Having established that a temporal reversal can occur, the next step examined possible pharmacological reversal. The tachykinin NK1 receptor antagonist, CP-96,345, produced a minor increase in withdrawal thresholds in animals with the cuff left permanently implanted. To determine the effect of early and repeated administration of CP-96,345, it was given daily on days 1–4. The cuff was removed on day 4. Six days later, readings showed reversal of tactile hypersensitivity. We suggest that persistent neuropathic pain occurs from processes that develop over several hours and days, and that some of these processes may be prevented by early medical intervention. Thus, nerve injury in the context of chronic neuropathic pain should be treated in a similar manner to nerve injury resulting from stroke, spinal cord injury, and other types of neurotrauma. We suggest that effective medical intervention within the first few hours after nerve injury may spare a patient from a chronic debilitating pain that may be refractory to later therapies

Cannabinoid receptors in animal models of acute, tonic and chronic pain

The aim of the work presented here is to evaluate the effects of cannabinoids in three animal models of pain: acute, tonic and chronic. The tail flick test (acute pain) was used to test the effect of the cannabinoid agonist, WIN 55,212--2, on tail withdrawal latency from a noxious radiant heat source. It was also tested on the allodynia induced by either endogenous release or exogenous administration of substance P. WIN 55,212--2 was antinociceptive in this test, and blocked the substance P-induced allodynia, suggesting a post-synaptic site of action. The formalin test (tonic pain) was used to test the effects of the endogenous cannabinoid agonist, anandamide and the cannabinoid receptor antagonist AM 281. Anandamide was antinociceptive (with a short duration of action), and AM 281 was pronociceptive. When administered concomitantly, AM 281 blocked the effects of anandamide. When given alone and in the absence of a noxious stimulus, AM 281 was without effect. (Abstract shortened by UMI.