Neuropathic pain is not well understood. Although central dorsal horn remodelling is likely important in maintaining chronic neuropathic pain, afferent activity from injured nerves or ganglia may initiate these changes. It is suggested, in this review that the peripheral nerve trunk is capable of sustaining a "flare" response as observed in injured skin and other tissues. The injury response may be associated with local vasodilatation, plasma extravasation and the generation of painful local afferent activity sustained by locally originating peptidergic fibers (nervi nervorum). These fibers contain substance P, calcitonin gene-related peptide and other peptides that have been linked to nociceptive transmission. Manipulation of the local injury response of the nerve trunk by pharmacologic means may provide one strategy in the treatment of neuropathic pain.