• Weiya Ma, Yong Zhang, Carsten Bantel, and James C Eisenach.
• Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1009, USA.
• Pain. 2005 Feb 1;113(3):386-94.

AbstractSome electrophysiologic studies demonstrate new, excitatory alpha2-adrenoceptors on peripheral nociceptors and their dorsal root ganglion (DRG) cell bodies after nerve injury, yet administration of alpha2-adrenoceptor agonists at these sites reduces hypersensitivity rather than worsens it. Since TRPV-1 expressing nociceptor afferents are important in many pain states, we examined the expression of this channel and its co-expression with alpha2C-adrenoceptors in injured DRG cell bodies and the ability of alpha2-adrenoceptors to inhibit responses to stimulation. Rats underwent tight ligation of the left L5 and L6 spinal nerves, followed by behavioral testing, removal of L5 and L6 DRGs, and either immunostaining for TRPV-1 channels and alpha2C-adrenoceptors or intracellular calcium videomicroscopy in response to electrical field stimulation before and after perfusion with clonidine and capsaicin. Spinal nerve ligation produced tactile allodynia. In normal and sham controls, about one-third of DRG neurons were TRPV-1-immunoreactive (IR), one half were alpha2C-adrenoceptor-IR and one-fourth co-expressed both. After nerve ligation there was a reduction in the number of small, strongly TRPV-1-IR or alpha2C-adrenoceptor-IR neurons, but an increase in medium and large, lightly stained cells and in their co-expression. The proportion of clonidine inhibited cells which responded to capsaicin increased 5 fold after injury. We conclude that TRPV-1 and alpha2C-adrenoceptors are up-regulated in some injured medium and large size neurons after nerve ligation. Increased co-expression by immunocytochemistry, and increased proportion of cells inhibited by clonidine and expressing functional TRPV-1 channels suggest that these cells may play an important role in the analgesic effects of alpha2-adrenoceptor agonists in neuropathic pain.

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