An animal model of painful peripheral neuropathy is produced in the rat by a chronic constriction injury to the sciatic nerve. Animals with this nerve injury have behavioral symptoms that indicate disordered pain sensations like those seen in human syndromes. In particular, the rats have hyperalgesia to thermal and mechanical stimuli, allodynia (pain from normally innocuous stimuli) to touch, and spontaneous pain (or dysesthesias). The nerve injury is known to cause transsynaptic degeneration in small, presumably inhibitory, interneurons in laminae I- III, and this is believed to be due to a NMDA receptor-mediated excitotoxic effect of spontaneous discharge from the damaged primary afferent neurons. Recent work shows that an ordinary surgical incision (without intentional nerve damage) has a similar effect. In this case, the functional impairment of the damaged cells may contribute to postoperative pain and tenderness. Dextrorphan, an NMDA blocker, has been shown to block the rats' heat-hyperalgesia, while having little or no effect on mechano-hyperalgesia and -allodynia. Morphine has a different effect: reduction of mechano-hyperalgesia and -allodynia with little or no effect on heat-hyperalgesia. Perineural corticosteriod treatment produces a marked deficit in heat-hyperalgesia, but with little effect on mechano-hyperalgesia and -allodynia. These data indicate the potential usefulness of morphine, perineural corticosteriods, and NMDA blockers in the treatment of neuropathic pain and support our hypothesis that the different kinds of abnormal pain symptoms seen in the clinic may be caused by different pathophysiologic mechanisms; thus indicating the potential need for combination drug treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000413-08
Application #
3775664
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code