Link between skin innervation and neuropathic pain

Nerve conduction studies for large-diameter motor and sensory nerves were normal. This report documents a pure small-fibre sensory neuropathy after prolonged use of linezolid, and the relationship between skin innervation and corresponding neuropathic pain.

Journal of Neurology, Neurosurgery, and Psychiatry 2008;79:97-99

The sympathetic system is responsible for the physiological responses to emotional states

The common epithet of “fight or flight” is being enlarged to be “fight, flight, or fright” or even “fight, flight, fright, or freeze.” Cannon’s original contribution was a catchy phrase to express some of what the nervous system does in response to a threat, but it is incomplete. The sympathetic system is responsible for the physiological responses to emotional states. The name “sympathetic” can be said to mean that (sym- = “together”; -pathos = “pain,” “suffering,” or “emotion”).
http://cnx.org/content/m46582/latest/?collection=col11496/latest

Ablation of the sympathetic nervous system is a standard model for the study of sympathetic nervous system regulation of immune function

Ablation of the sympathetic nervous system by chemical sympathectomy is a standard model for the study of sympathetic nervous system regulation of immune function. We have previously documented that chemical denervation results in enhanced antigen-specific, but suppressed mitogen-induced, cytokine production by spleen cells. In our investigation into the mechanisms of sympathectomy-induced immune alterations, we first evaluated the peritoneal environment into which the protein antigen keyhole limpet hemocyanin is administered. Denervation resulted in increased production of tumor necrosis factor- by peritoneal exudate cells and these cells appeared to have enhanced antigen presenting capability. We hypothesized that nerve terminal destruction may be inducing an inflammatory response by monocyte/macrophages and other cell types throughout the periphery that could differentially alter subsequent mitogen versus antigen-specific responses. However, no evidence of sympathectomy-induced systemic or local splenic inflammatory responses was observed, as indicated by measuring the proinflammatory cytokines tumor necrosis factor- and interleukin-1. These experiments indicate that an inflammatory response is not likely to be responsible for sympathectomy-induced immune alterations, eliminating a potential confounding factor in interpreting sympathectomy studies. Copyright 2001 Elsevier Science (USA).

Authors: Callahan T.A.^{1, 2}; Moynihan J.A.^{1, 2, 3, 4, 5}
Source: Brain, Behavior, and Immunity, Volume 16, Number 1, February 2002 , pp. 33-45(13)

Following a peripheral nerve injury, a sterile inflammation develops in sympathetic and dorsal root ganglia

Following a peripheral nerve injury, a sterile inflammation develops in sympathetic and dorsal root ganglia (DRGs) with axons that project in the damaged nerve trunk. Macrophages and T-lymphocytes invade these ganglia where they are believed to release cytokines that lead to hyperexcitability and ectopic discharge, possibly contributing to neuropathic pain. Here, we examined the role of the sympathetic innervation in the inflammation of L5 DRGs of Wistar rats following transection of the sciatic nerve, comparing the effects of specific surgical interventions 10-14days prior to the nerve lesion with those of chronic administration of adrenoceptor antagonists. Immunohistochemistry was used to define the invading immune cell populations 7days after sciatic transection. Removal of sympathetic activity in the hind limb by transecting the preganglionic input to the relevant lumbar sympathetic ganglia (ipsi- or bilateral decentralization) or by ipsilateral removal of these ganglia with degeneration of postganglionic axons (denervation), caused less DRG inflammation than occurred after a sham sympathectomy. By contrast, denervation of the lymph node draining the lesion site potentiated T-cell influx. Systemic treatment with antagonists of α1-adrenoceptors (prazosin) or β-adrenoceptors (propranolol) led to opposite but unexpected effects on infiltration of DRGs after sciatic transection. Prazosin potentiated the influx of macrophages and CD4+ T-lymphocytes whereas propranolol tended to reduce immune cell invasion. These data are hard to reconcile with many in vitro studies in which catecholamines acting mainly via β2-adrenoceptors have inhibited the activation and proliferation of immune cells following an inflammatory challenge.
Auton Neurosci. 2013 Dec 23.
http://www.ncbi.nlm.nih.gov/pubmed/24418114

Surgical sympathectomy is rarely performed and its use remains controversial

Although improved in some, persistent or recurrent symptoms were present in all patients after six months postoperatively. Increased sensitivity of digital vessels to circulating catecholamines, nerve fiber regeneration or incomplete sympathectomy have been postulated to lead to recurrence. Five patients developed Horner's syndrome postoperatively. A portion of the stellate ganglion was intentionally resected in 3 of the 5 patients.
http://www.ncbi.nlm.nih.gov/pubmed/8370999

"synaptic reorganization in the sympathetic chain or spinal cord after sympathotomy"

http://www.mayoclinic.org/documents/mc5520-06pdf/DOC-20077566

increase in total blood flow represents, in the main, arteriovenous shunting with a little, if any effect on the nutritive blood flow at the tissue level

Lumbar sympathectomy is widely used in the treatment of peripheral vascular disease involving the lower extremity. The obvious increase in skin temperature postoperatively has led to the belief that there is a concommitant increase in perfusion of all tissues in the leg. 

Recent evidence suggests that this increase in total blood flow represents, in the main, arteriovenous shunting with a little, if any effect on the nutritive blood flow at the tissue level. Studies aimed at investigating the effect of lumbar sympathectomy on regional tissue circulation have utilized the local clearance of radioactive isotopes. No significant change in the clearance of these substances in muscle have been noted following lumbar sympathectomy in man.

Tissue Blood Flow in the Canine Lower Limb Following Lumbar SympathectomyVASC ENDOVASCULAR SURG November 1972 6: 227-238,

prolongation of the isometric (tension) period (TP) of the left ventricle occurred in the majority (72 per cent) of all cases after sympathectomy

The prolongation of the isometric (tension) period (TP) of the left ventricle which occurred in the majority (72 per cent) of all cases after unilateral or bilateral transthoracic sympathectomy (without or with unilateral or bilateral transthoracic splanchnicotomy) indicates a diminution of inotropic cardiac action. It can be assumed to correspond to the cholinergic (vagal) preponderance which results from a partial or complete sympathetic denervation of the heart. Reduction of the pulse pressure oc-

curred in 56 per cent of the cases, probably due to the same mechanism.

www.chestjournal.org/content/38/4/423.full.pdfby W RAAB - 1960