Spatial patterns of spinal cord [ 14C]-2-deoxyglucose metabolic activity in a rat model of painful peripheral mononeuropathy

Abstract

Spatial patterns of spinal cord glucose metabolic activity were examined in unanesthetized rats with painful peripheral mononeuropathy produced by sciatic nerve ligation (chronic constrictive injury, CCI). Spinal cord metabolic activity was assessed 10 days after nerve ligation by using the fully quantitative [ 14C]-2-deoxyglucose technique. This technique allows simultaneous examination of both neural activity inferred from local glucose utilization and its spatial distribution in multiple spinal regions previously implicated in nociceptive processing. Rats used in the experiment exhibited thermal hyperalgesia to radiant heat applied to the hind paw ipsilateral to nerve ligation and behaviors indicative of spontaneous pain. Sciatic nerve ligation produced a significant increase in spinal cord metabolic activity in four sampling regions (laminae I–IV, V–VI, VII and VIII–IX) of lumbar segments compared to sham-operated rats. The pattern of altered metabolic activity in CCI rats presented 3 distinct features. 1. (1) The spinal cord grey matter both ipsilateral and contralateral to nerve ligation exhibited substantial increases in metabolic activity compared to sham-operated rats. 2. (2) This increase in metabolic activity was somatotopically specific i.e., higher metabolic rates were observed on the side ipsilateral to nerve ligation than on the contralateral side, and higher metabolic rates were seen in the medial portion of the ipsilateral spinal cord dorsal horn than in the lateral portion. The peak metabolic activity occurred in laminae V–VI of CCI rats, a region involved in nociceptive processing. 3. (3) The increase in spinal cord metabolic activity of CCI rats extended from lumbar segment L 1 to L 5 in all 4 sampling regions. The substantial increase in metabolic activity in both the ipsilateral and contralateral spinal cord that occurs over an extensive rostro-caudal area in CCI rats may represent a unique pattern of spinal cord metabolic activity distinct from that observed in rats exposed to acute thermal pain. This pattern of spinal cord neural activity in CCI rats may reflect possible radiation of neuropathic pain. In addition, the procedure of curare-induced paralysis in a separate group of CCI rats did not change the extent and patterns of metabolic activity seen in non-paralyzed CCI rats, reflecting a minimal influence of the afferent feedback from flexor motor reflexes on spinal cord metabolic activity following sciatic nerve ligation. This chronic increase in spinal cord neural activity in the absence of overt peripheral stimulation suggests a spinal cord hyperactive state and may account for behaviors suggestive of spontaneous pain in CCI rats. These results provide the first description of the spatial patterns of spinal cord neural activity (inferred from spinal cord glucose metabolism) in neuropathic rats. In addition, these data should provide insights into neural mechanisms underlying human neuropathic pain and possibly other chronic pain syndromes in man.