Extra-territorial pain in rats with a peripheral mononeuropathy: mechano-hyperalgesia and mechano-allodynia in the territory of an uninjured nerve

TLDR

Peripheral neuropathies can produce pain outside nerve territories, a phenomenon termed extra‑territorial pain that has been cited as evidence for psychogenic disorders. The study used a unilateral chronic constriction injury of the sciatic nerve in rats. From day 1 to 18, rats exhibited mechano‑hyperalgesia in both the injured sciatic and uninjured saphenous territories; from day 4 onward, mechano‑allodynia developed in both territories with similar severity and time course, and transection of the saphenous nerve abolished allodynia in its territory but not sciatic, while sciatic transection abolished allodynia in the sciatic territory but not saphenous, demonstrating extra‑territorial pain in rats analogous to humans and suggesting a central pain‑processing dysfunction.

Abstract

The abnormal pain sensations that accompany peripheral neuropathies are sometimes found in a distribution that does not coincide with the territories of nerves or posterior roots. This ‘extra-territorial’ pain is one of the lines of evidence that has been advanced to support the proposal that these patients suffer from a psychogenic disorder. In the present experiments, rats were prepared with a unilateral chronic constriction injury (CCI) to the sciatic nerve. Beginning on the first postoperative day and continuing for at least 18 days, exaggerated withdrawal reflexes to pinprick stimulation, indicative of mechano-hyperalgesia, were seen on the side of nerve injury in the hindpaw territories of both the injured sciatic nerve and the uninjured saphenous nerve. Beginning on postoperative day 4 and continuing for at least the next 3 weeks, the withdrawal responses to von Frey hair stimulation on the nerve-injured side occurred at a significantly lower threshold, indicating the presence of mechano-allodynia. The severity and time course of the mechano-allodynia were similar in both nerve territories. When tested 18 days after the CCI, mechano-allodynia in the saphenous territory was abolished by an acute saphenous transection, but unaffected by sciatic transection. Conversely, mechano-allodynia evoked from the mid-plantar sciatic territory was abolished by acute sciatic transection, but unaffected by saphenous transection. These results show that rats with an experimental painful peripheral mononeuropathy have extra-territorial pain like that seen in man. Extra-territorial pain may be partly or entirely due to a peripheral nerve injury-evoked dysfunction of pain processing neurons in the central nervous system.