Sympathetic sprouting and changes in nociceptive sensory innervation in the glabrous skin of the rat hind paw following partial peripheral nerve injury

Abstract

Previous studies have suggested that sympathetic sprouting in the periphery may contribute to the development and persistence of sympathetically maintained pain in animal models of neuropathic pain. In the present study, we examined changes in the cutaneous innervation in rats with a chronic constriction injury to the sciatic nerve. At several periods postinjury, hind paw skin was harvested and processed by using a monoclonal antibody against dopamine‐β‐hydroxylase to detect sympathetic fibers and a polyclonal antibody against calcitonin gene‐related peptide to identify peptidergic sensory fibers. We observed migration and branching of sympathetic fibers into the upper dermis of the hind paw skin, where they were normally absent. This migration was first detected at 2 weeks, peaked at 4–6 weeks, and lasted for at least 20 weeks postlesion. At 8 weeks postlesion, there was a dramatic increase in the density of peptidergic fibers in the upper dermis. Quantification revealed that densities of peptidergic fibers 8 weeks postlesion were significantly above levels in sham animals. The ectopic sympathetic fibers did not innervate blood vessels but formed a novel association and wrapped around sprouted peptidergic nociceptive fibers. Our data show a long‐term sympathetic and sensory innervation change in the rat hind paw skin after the chronic constriction injury. This novel fiber arrangement after nerve lesion may play an important role in the development and persistence of sympathetically maintained neuropathic pain after partial nerve lesions. J. Comp. Neurol. 495:679–690, 2006. © 2006 Wiley‐Liss, Inc.

Long‐Term Effects of Neonatal Capsaicin Treatment on Intraepidermal Nerve Fibers and Keratinocyte Proliferation in Rat Glabrous Skin

“…Moreover, additional sensory alterations may come from the fact that ample zones of epidermis were devoid of innervation in treated rats. Recently, it has been shown that a lesion of sensory nerves lead to aberrant sprouting of sympathetic fibers into the upper dermis of the rat (Yen et al, 2006). We observed such aberrant dopamine-b-hydorxylase imunoreactive fibers in the dermal-epidermal border and also noted some fibers penetrating the epidermis in capsaicin rats of ages 3 M and 6 M (Supporting Information Fig.…”

“…The rodent hind paw skin has been frequently used as an experimental model to study nerve degeneration and regeneration (Navarro et al, 1995;Ma and Bisby, 2000;Yen et al, 2006). However, there is little published quantitative data about the development of epidermal innervation in this skin region.…”

Paclitaxel- and vincristine-evoked painful peripheral neuropathies: Loss of epidermal innervation and activation of Langerhans cells

“…Normal rats do not have any sympathetic post-ganglionic fibers in the hind paw plantar epidermis (Yen et al, 2006).…”

Inflammation in CRPS: Role of the sympathetic supply

“…Besides injury-induced expression of novel adrenergic receptors, sprouting of sympathetic fibers occurs in the skin after chronic constriction injury of the sciatic nerve (Yen et al, 2006). In animal models of peripheral nerve lesions, sympathetic nerve sprouting was also detected in the dorsal root ganglia (DRG) and these sympathetic fibers formed baskets around large primary neuronal cell bodies (Gibbs et al 2008;McLachlan et al, 1993;Pertovaara, 2006), of non-nociceptive A-fibers (Michaelis et al, 1996).…”