Sensitization of Cutaneous Nociceptors in Neuropathic Rats

Shim, Beom; Gwak, Young Seob; Yoon, Duck Mi; Leem, Joong Woo; Nam, Taick Sang; Paik, Kwang Se

Abstract

BACKGROUND: Peripheral nerve injury leads to neuropathic pain. Although it has been accepted that both peripheral and central processes may play a role in the pathophysiology of these sensory abnormalities, the involvement of peripheral mechanisms is often overlooked. The present study was conducted using neuropathic rats to see if cutaneous nociceptors were sensitized and developed adrenergic sensitivity after peripheral nerve injury.
METHODS
Single fiber recording technique was used to record the neural activity of nociceptive fibers in sural or plantar nerves of control rats and of rats that had previously received the L5-L6 spinal nerve ligation (neuropathic rats). Mechanical and heat thresholds of the recorded fibers were determined using von Frey filaments and thermal stimulators, respectively, which were applied to somatic receptive fields. Responses to suprathreshold mechanical and heat stimuli were also studied. The adrenergic sensitivity of nociceptive fibers was investigated by injecting intra-arterially the alpha-adrenergic agonist, phenylephrine.
RESULTS
Both mechanical and heat thresholds of nociceptive fibers in neuropathic rats were significantly lowered than those in control rats. In responses to suprathreshold stimuli, neuropathic nociceptive fibers had higher mechanical-suprathreshold responses than control nociceptive fibers, while their heat-suprathreshold responses were not significantly different from those of control rats. About 10% of sampled nociceptive fibers in neuropathic rats responded to phenylephrine.
CONCLUSIONS
The results suggest that nociceptors on the skin supplied by injured nerves are sensitized to both mechanical and heat stimuli, and develop adrenergic sensitivity following peripheral nerve injury. The sensitization and adrenergic sensitivity of cutaneous nociceptors may play a role, in part, in the development of neuropathic pain.