A single GABA neuron receives contacts from myelinated primary afferents of two adjacent peripheral nerves. A possible role in neuropathic pain. Issue 18 (19th November 2018)

• Record Type: Journal Article
• Authors: Shehab, Safa; Rehmathulla, Sumisha; Javed, Hayate
• Is Part Of: Journal of comparative neurology. Volume 526:Issue 18(2018)
• Page Start: 2984
• Page End: 2999
• Publication Date: 2018-11-19
• Subjects: GABA neurons -- L4 and L5 nerves -- neuropathic pain -- primary afferents -- spinal cord -- AB_300798 -- AB_2338952 -- AB_258833 -- AB_10013220 -- AB_2314660 -- AB_2571774; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.24509
• Languages: English
• ISSNs: 0021-9967

Abstract

Abstract: GAD67‐EGFP mice were used in a series of experiments to provide anatomical evidence for the role of the reduction in myelinated primary afferent input to GABA spinal neurons in the production of neuropathic pain following peripheral L5 nerve injury. First, we confirmed that L5 injury in these mice produced mechanical and thermal hyperalgesia in the ipsilateral foot. Second, we injected a mixture of cholera toxin subunit‐B (CTb) and isolectin B4 (IB4) in the sciatic nerve to selectively label its myelinated and unmyelinated primary afferents. Results showed that primary afferents of sciatic nerve extend from L2‐L6 spinal segments. Third, we determined the central terminations of myelinated primary afferents of L4 and L5 spinal nerves following CTb injection in either nerve. The myelinated primary afferents of both nerves terminated in the corresponding and two to three rostral spinal segments with some fibers descending to terminate in the segment caudal to the level at which they entered indicating an intermingling of their terminals at the dorsal horn of the spinal cord. Fourthly, we injected CTb in L5 nerve and CTb HRP‐conjugate in L4 nerve. Confocal microscopy and subsequent image analyses showed that individual EGFP‐labeled neurons in L4 segment receive myelinated primary afferent contacts from both L4 and L5 nerves. Eliminating inputs from L5 nerve following its injury would result in less involvement of spinal GABA neurons which would very likely initiate neuronal sensitization in L4 segment. This could lead to the development of hyperalgesia in response to the stimulation of the adjacent uninjured L4 nerve. Abstract : GABA neuron 1 receives myelinated afferents from L4 and L5 nerves. Injury of the L5 nerve would reduce the excitatory input to the inhibitory (GABAergic) interneurons. This will lead to the reduction in the inhibitory drive to projection neurons (green) in the L4 segment which would cause spinal neuronal sensitization potentially contributing to the production of hyperalgesia.