Effects of lumbar sympathectomy on pain behavioral changes caused by nucleus pulposus-induced spinal nerve damage in rats

Abstract

IntroductionIt has been reported that nucleus pulposus in the epidural space induces spinal nerve root damage, not only by mechanical but also by chemical mechanisms as nucleus pulposus is capable of producing proinflammatory cytokines [5,14,16,17,19,21,23,29]. There have been a number of recent reports regarding the pain behavior due to lumbar disk herniation in rats [7,18,20,24]. One well-characterized model involves L4/5 disk incision and/or displacement of the adjacent spinal nerve in rats. These studies indicated that the combination of chemical and mechanical damage results in behavioral changes, mechanical allodynia, thermal hyperalgesia, increased lifting of the hind paw on the operated side, and increased rotation of the head toward the operated side [18].Tight and loose ligation with or without transection of the nerve are well-known neuropathic pain models in rats [1,9]. These models show mechanical allodynia and thermal hyperalgesia. It has been reported that lumbar sympathectomy, which was performed in these pain models, can decrease the pain behavior [2,8,10]. Kim et al. reported the prevention of pain behavioral changes by sympathectomy prior to nerve ligation [10]. In contrast, it has also been reported that intraperitoneal injection of phentolamine hydrochloride, an alphaadrenoceptor blocker, or surgical sympathectomy does Abstract It has been suggested that lumbar sympathectomy can reduce pain behavior, including mechanical allodynia and thermal hyperalgesia, caused by ligation of the spinal nerve. One well-characterized model, which involves application of nucleus pulposus to the spinal nerve and displacement of the adjacent nerve, shows behavioral changes in rats. However, there have been no previous reports regarding sympathectomy performed in this model. Disk incision and adjacent spinal nerve displacement were performed with (n=6) or without (n=6) sympathectomy. Sham surgery was also performed with (n=6) or without (n=6) sympathectomy. The animals were tested for 3 days before surgery and on days 1, 3, 7, 14, and 21 after surgery. Non-noxious mechanical thresholds were tested by determining the hind paw withdrawal response to von Frey hair stimulation of the plantar surface of the footpad using a touch stimulator. Thermal nociceptive thresholds were tested using a sensitive thermal-testing device. While rats in the disk incision with displacement surgery group showed allodynia and hyperalgesia after surgery on the experimental side, sympathectomized animals did not. No allodynia was observed in the sham groups. Sympathectomy seemed to prevent the pain behavioral changes caused by the combination of disk incision and nerve displacement.

Sympathectomy Reduces Mechanical Allodynia, Tumor Necrosis Factor-Alpha Expression, and Dorsal Root Ganglion Apoptosis Following Nerve Root Crush Injury

“…It has also been reported that unilateral sympathectomy 1 day before spinal nerve damage prevents pain behavior changes. 11 In the present study, our results suggest that unilateral sympathectomy just before nerve injury can prevent the development of mechanical allodynia. The threshold showed high variability in the sympathectomy and sham groups compared with the crush group.…”

Sympathectomy attenuates excitability of dorsal root ganglion neurons and pain behaviour in a lumbar radiculopathy model

“…Meanwhile, several studies have also reported that sympathectomy reduces mechanical allodynia and thermal hyperalgesia in various animal pain models. 2,8,17 Clinical reports have shown that a sympathetic nerve block reduces lumbar radicular pain 28,29 and sympathectomy increases intraradicular, 30 cauda equina, 31 and sciatic nerve blood flow. 32 It has also been suggested that the recovery of reduced DRG blood flow might prevent allodynia in a radicular pain model.…”

“…32 It has also been suggested that the recovery of reduced DRG blood flow might prevent allodynia in a radicular pain model. 8 Sekiguchi et al 2 reported that sympathectomy reduced mechanical allodynia, tumor necrosis factor-alpha (TNF-α) expression, and DRG neuron apoptosis following nerve root crush injury. 2 Chen et al 17 showed that surgical and chemical sympathectomy significantly attenuated bee venom-induced mechanical hyperalgesia and inflammatory response.…”

“…2,8,13,14,17 In contrast, some animal studies have reported that sympathectomy does not reduce allodynia and hyperalgesia. 18-21 In addition, a clinical report demonstrated that the placebo effect of phentolamine, a sympathetic blocker for painful polyneuropathies, was responsible for pain relief.…”

Does Norepinephrine Influence Pain Behavior Mediated by Dorsal Root Ganglia?: A Pilot Study

“…Mizuno et al reported sympathetic nerve fibers increased in corresponding DRG neurons in the root constriction model [30]. Sympathectomy alleviates pain behaviors such as mechanical allodynia and thermal hyperalgesia in animal models [20,24,30,31,37]. In clinical cases, lumbar sympathetic block has been performed to relieve chronic pain, including intractable lumbar radicular pain [6,32,46].…”