Animal Models of Neuropathic Pain Induce Apoptosis and a Loss of GABAergic Inhibition in the Spinal Dorsal Horn

摘要

Neuropathic pain is a frequent complication in a variety of clinical conditions including infections, metabolic diseases, and traumatic injuries of peripheral nerves or the central nervous system (Koltzenburg 1998). As analgesic drugs are only partially effective, neuropathic pain represents a therapeutic challenge, particularly because it persists chronically in the majority of patients (Woolf and Mannion 1999). In some cases, the persistence of neuropathic pain may be related to the underlying etiology, for example in conditions like diabetes mellitus, but it is unclear why pain becomes chronic after traumatic nerve damage or persists after the reactivation of Varicella zoster virus in postherpetic neuralgia. We have investigated the hypothesis that decreased inhibition of afferent input in the spinal dorsal horn promotes neuropathic pain by allowing unchecked nociceptive transmission, and have attempted to determine whether reduced inhibition is attributable to the death of inhibitory interneurons. A loss of inhibitory interneurons would represent a permanent change and hence provide an explanation for ongoing pain after nerve injury.