Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury

Authors

Supinder S Bedi
Qing Yang
Robyn J Crook
Junhui Du
Zizhen Wu
Harvey M Fishman
Raymond J Grill
Susan M Carlton
Edgar T Walters

Publication Date

11-3-2010

Journal

Journal of Neuroscience

Abstract

Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs in nociceptors in vivo are unknown. We show that small DRG neurons from rats (Rattus norvegicus) receiving thoracic spinal injury 3 d to 8 months earlier and recorded 1 d after dissociation exhibit an elevated incidence of SA coupled with soma hyperexcitability compared with untreated and sham-treated groups. SA incidence was greatest in lumbar DRG neurons (57%) and least in cervical neurons (28%), and failed to decline over 8 months. Many sampled SA neurons were capsaicin sensitive and/or bound the nociceptive marker, isolectin B4. This intrinsic SA state was correlated with increased behavioral responsiveness to mechanical and thermal stimulation of sites below and above the injury level. Recordings from C- and Aδ-fibers revealed SCI-induced SA generated in or near the somata of the neurons in vivo. SCI promotes the entry of primary nociceptors into a chronic hyperexcitable-SA state that may provide a useful therapeutic target in some forms of persistent pain.

Keywords

Action Potentials, Animals, Behavior, Animal, Cells, Cultured, Chronic Disease, Disease Models, Animal, Female, Ganglia, Spinal, Male, Nociceptors, Pain, Pain Measurement, Physical Stimulation, Rats, Rats, Sprague-Dawley, Sensory Receptor Cells, Spinal Cord Injuries