Contributions of injured and intact afferents to neuropathic pain in an experimental rat model

Abstract

This study was conducted to determine the contribution of peripheral inputs from injured and intact afferent fibers to behavioral signs of neuropathic pain, using a previously developed neuropathic rat model. Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves; this procedure induced rats to display neuropathic pain behaviors in the ipsilateral hindlimb. The behaviors included signs of mechanical and cold allodynia, as well as ongoing pain. Five days after neuropathic injury, peripheral inputs from injured segments (L5 and L6) or intact segments (L3 and L4) were blocked by either transection of the dorsal roots or application of a local anesthetic (bupivacaine) to the roots. Dorsal rhizotomy of the injured segments reduced all components of neuropathic pain behaviors. In contrast, dorsal rhizotomy of the uninjured segments abolished behavioral signs of mechanical and cold allodynia, but signs of ongoing pain were preserved. Blocking afferent inputs by application of bupivacaine mimicked the results of dorsal rhizotomy, in a reversible manner. These results suggest that afferent signals from injured and intact fibers play distinctively different roles in neuropathic pain: inputs from injured afferents maintain all components of neuropathic pain, while those from intact afferents mediate evoked pain such as mechanical and cold allodynia. An hypothesis is proposed to explain the results of the present as well as other published studies.

Role of Mitogen-Activated Protein Kinase Activation in Injured and Intact Primary Afferent Neurons for Mechanical and Heat Hypersensitivity after Spinal Nerve Ligation

“…The present study demonstrated that in the injured L5 DRG, most of the p-ERK-IR neurons and a subpopulation of p-p38-IR neurons were large in size and that the ERK and p38 inhibitors reversed the L5 SNL-induced mechanical allodynia. Furthermore, L5 dorsal rhizotomy prevented the development of mechanical allodynia, as reported previously (Yoon et al, 1996;Sukhotinsky et al, 2004). These observations support the possibility that large-diameter A-fibers mediate mechanical allodynia, whereas nociceptive C-fibers mediate thermal hyperalgesia Pan et al, 2003).…”

Spontaneous Pain, Both Neuropathic and Inflammatory, Is Related to Frequency of Spontaneous Firing in Intact C-Fiber Nociceptors

“…Spontaneous foot-lifting duration was measured as the cumulative duration in seconds for which rats lifted their ipsilateral hindfoot accompanied often by aversive behavior (e.g., foot shaking/licking) over 5 min. Foot lifting associated with exploratory behavior, locomotion, body repositioning, and grooming was excluded (Yoon et al, 1996). This was repeated twice (10 min total time) with an interval of 5 min.…”

At-level neuropathic pain is induced by lumbosacral ventral root avulsion injury and ameliorated by root reimplantation into the spinal cord

“…There is also evidence that these adjacent, uninjured afferents may contribute to the development and maintenance of neuropathic pain (Wu et al, 2001, Gold et al, 2003, Lee et al, 2003. One proposed mechanism is that Wallerian degeneration in mixed roots may result in the release of degenerative by-products and subsequent changes in the cellular and electrophysiological properties of the adjacent uninjured afferents, thereby resulting in pain (Yoon et al, 1996, Li et al, 2000. In the present model, for example, as the L6 fibers travel with L5 afferents to some degree in the sciatic nerve, it is possible that by-products of L6 efferent axonal degeneration may affect the functional properties of the L5 afferents (Wu et al, 2001).…”