Sympathetic sprouting in the dorsal root ganglia of the injured peripheral nerve in a rat neuropathic pain model

Abstract

The extent of the sprouting of sympathetic postganglionic fibers in the dorsal root ganglion (DRG) and the peripheral nerves was examined in neuropathic rats at different postoperative times. After the L5 and L6 spinal nerves were ligated on one side, three different pain behavior tests (representing mechanical allodynia, cold allodynia, ongoing pain exacerbated by cold stress) were performed at various time intervals. The sympathetic postganglionic fibers were visualized by immunostaining with antibodies to tyrosine hydroxylase (TH). In the neuropathic rats, all three pain behaviors were fully developed within 3 days after the surgery, maintained up to 2 weeks, and then started to decline gradually afterward. At 20 weeks after neuropathic surgery, pain behaviors were reduced significantly compared to the peak response, but were still higher than the presurgery levels. Sympathectomy, performed 4 days after neuropathic surgery, almost completely abolished the signs of mechanical allodynia and ongoing pain behaviors, and it reduced the behaviors of cold allodynia to approximately half. The numerical density of sympathetic fibers in the DRG of an injured segment was significantly higher at 1, 4, and 20 weeks after neuropathic surgery as compared to the normal, suggesting that there is sprouting of sympathetic fibers in the DRG after peripheral nerve injury. Sprouting of sympathetic fibers in the DRG was extensive as early as 2 days after the spinal nerve ligation, and the sprouted fibers were almost completely eliminated after sympathectomy. The data suggest that sympathetic innervation of the DRG may play an important role in the development and maintenance of sympathetically maintained neuropathic pain.

Morphological and Functional Roles of Macrophages and Postganglionic Sympathetic Fibers in Dorsal Root Ganglions of a Rat Neuropathic Pain Model.

“…The mechanisms of neuropathic pain include spinal sensitization caused by the input of ectopic discharges arising from injured sensory neurons [12] through NMDA receptor activation [15], alterations in neuropeptide levels in the spinal cord [17], myelinated axons sprouting into the second lamina of the spinal cord [45], and cross-talk between sensory and sympathetic nerves [9,10,25]. The interaction between sensory and sympathetic nervous systems is thought to be the most important factor in the mechanisms of SMP.…”

“…After peripheral nerve injury, postganglionic sympathetic fibers sprout into the DRG neuronal area [9,10,25] and surround DRG neurons; some of these fibers make direct contact with DRG neurons [8]. The postganglionic sympathetic fibers which directly contact DRG neurons release catecholamines and other modulators, and these contacts might induce hypersensitivity of postsynaptic DRG neurons, because the symptoms of SMP never develop when the sympathectomy is carried out before ligating spinal nerves [20].…”

“…After sympathectomy the symptoms of neuropathic pain disappear or fail to develop when the sympathectomy is carried out before lesion of the spinal nerves [7,18,20,30,31,38]. After peripheral nerve injury, postganglionic sympathetic fibers sprout into regions around dorsal root ganglion (DRG) neurons [9,10,25], and make direct contact with the DRG neurons [8].…”

Neuropathic pain: a practical guide for the clinician

“…The importance of the sympathetic nervous system in neuropathic pain has been demonstrated by analgesia following sympathectomy in animals 71 and humans, 72 and by pain exacerbation through activation of the sympathetic nervous system. 73 Sympathetically maintained pain may be explained by sprouting of sympathetic neurons into dorsal root ganglia of injured sensory neurons 74 and postinjury sprouting of sympathetic fibres into the dermis.…”

Behavioral Models of Pain States Evoked by Physical Injury to the Peripheral Nerve

“…113,114 In addition, SNL induces sympathetic sprouting into the dorsal root ganglia. 115 However, the sympathetic component of the model has been disputed, 116 and the belief now is that the sympathetic component is influenced by not only the strain, but also, perhaps, by the vendor-dependent substrain. 117 Variables affecting ligation-evoked changes in pain thresholds have included gender.…”