Inflammatory hyperalgesia: a role for the C-fiber sensory neuron cell body?

Peripheral nerve injury increases the chemosensitivity and excitability of injured afferents, resulting in ectopic activity arising from within dorsal root ganglia. Studies of dissociated sensory ganglion neurons in vitro suggest afferent somata might be sensitized by persistent inflammation. However, it is unknown whether this inflammation-induced sensitization is manifest in somata within the intact ganglia. To explore this possibility, intracellular electrophysiologic recording was used with a sciatic nerve-L4-dorsal root ganglia preparation to compare excitability and chemosensitivity of cutaneous C-fiber somata from control and inflamed rats. Cutaneous afferents were identified with the retrograde dye DiI. Excitability was assessed before and after the application of inflammatory soup (IS) containing bradykinin, serotonin, and prostaglandin E2 all at a pH of 7.0. Persistent inflammation decreased the excitability of cutaneous afferents in intact ganglia and had no significant influence on the magnitude of IS-induced increase in excitability. Opposite to the effects observed in intact ganglia, excitability was greater in dissociated cutaneous nociceptors obtained from inflamed rats, although the magnitude of the IS-induced increase in excitability was not significantly affected by inflammation. These results suggest that the cell bodies of putative cutaneous nociceptors in the intact ganglia contribute minimally to pain and hyperalgesia associated with persistent inflammation.

Results of the present study suggest that inflammation-induced changes in afferent somata are minimal. However, they also suggest that inflammatory mediator-induced increase in the excitability of sensory neuron somata might contribute to global changes in nociception observed under high systemic inflammatory mediator loads.