A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury

Molecular Pain - Tập 7 - Trang 1-9 - 2011
Gila Moalem-Taylor1, Man Li2, Haydn N Allbutt3, Ann Wu1, David J Tracey1
1School of Medical Sciences, University of New South Wales, Sydney, Australia
2Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3Department of Physiology, University of Sydney, Australia

Tóm tắt

A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury. We found that a preconditioning crush injury to a terminal branch of the sciatic nerve seven days before partial ligation of the sciatic nerve (PSNL; a model of neuropathic pain) induced a significant attenuation of pain hypersensitivity, particularly mechanical allodynia. A preconditioning lesion of the tibial nerve induced a long-term significant increase in paw-withdrawal threshold to mechanical stimuli and paw-withdrawal latency to thermal stimuli, after PSNL. A preconditioning lesion of the common peroneal induced a smaller but significant short-term increase in paw-withdrawal threshold to mechanical stimuli, after PSNL. There was no difference between preconditioned and unconditioned animals in neuronal damage and macrophage and T-cell infiltration into the dorsal root ganglia (DRGs) or in astrocyte and microglia activation in the spinal dorsal and ventral horns. These results suggest that prior exposure to a mild nerve lesion protects against adverse effects of subsequent neuropathic injury, and that this conditioning-induced inhibition of pain hypersensitivity is not dependent on neuroinflammation in DRGs and spinal cord. Identifying the underlying mechanisms may have important implications for the understanding of neuropathic pain due to nerve injury.

Tài liệu tham khảo

Moalem G, Tracey DJ: Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev 2006, 51: 240–264. 10.1016/j.brainresrev.2005.11.004

McQuarrie IG, Grafstein B, Gershon MD: Axonal regeneration in the rat sciatic nerve: effect of a conditioning lesion and of dbcAMP. Brain Research 1977, 132: 443–453. 10.1016/0006-8993(77)90193-7

Neumann S, Woolf CJ: Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 1999, 23: 83–91. 10.1016/S0896-6273(00)80755-2

Richardson PM, Issa VM: Peripheral injury enhances central regeneration of primary sensory neurones. Nature 1984, 309: 791–793. 10.1038/309791a0

Neumann S, Bradke F, Tessier-Lavigne M, Basbaum AI: Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 2002, 34: 885–893. 10.1016/S0896-6273(02)00702-X

Gidday JM: Cerebral preconditioning and ischaemic tolerance. Nature Reviews Neuroscience 2006, 7: 437–448. 10.1038/nrn1927

Le Bars D, Dickenson AH, Besson JM: Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain 1979, 6: 283–304. 10.1016/0304-3959(79)90049-6

Danziger N, Gautron M, Le Bars D, Bouhassira D: Activation of diffuse noxious inhibitory controls (DNIC) in rats with an experimental peripheral mononeuropathy. Pain 2001, 91: 287–296. 10.1016/S0304-3959(00)00451-6

Benoliel R, Eliav E, Tal M: Strain-dependent modification of neuropathic pain behaviour in the rat hindpaw by a priming painful trigeminal nerve injury. Pain 2002, 97: 203–212. 10.1016/S0304-3959(01)00428-6

Moalem G, Xu K, Yu L: T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats. Neuroscience 2004, 129: 767–777. 10.1016/j.neuroscience.2004.08.035

Goldstein ME, House SB, Gainer H: NF-L and peripherin immunoreactivities define distinct classes of rat sensory ganglion cells. J Neurosci Res 1991, 30: 92–104. 10.1002/jnr.490300111

Lee JW, Siegel SM, Oaklander AL: Effects of distal nerve injuries on dorsal-horn neurons and glia: relationships between lesion size and mechanical hyperalgesia. Neuroscience 2009, 158: 904–914. 10.1016/j.neuroscience.2008.10.010

Bajrovic F, Sketelj J: Extent of nociceptive dermatomes in adult rats is not primarily maintained by axonal competition. Exp Neurol 1998, 150: 115–121. 10.1006/exnr.1997.6734

Ren K, Dubner R: Descending modulation in persistent pain: an update. Pain 2002, 100: 1–6. 10.1016/S0304-3959(02)00368-8

Przewlocki R, Przewlocka B: Opioids in neuropathic pain. Curr Pharm Des 2005, 11: 3013–3025. 10.2174/1381612054865055

Milligan ED, Watkins LR: Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 2009, 10: 23–36. 10.1038/nrn2533

Li M, Peake PW, Charlesworth JA, Tracey DJ, Moalem-Taylor G: Complement activation contributes to leukocyte recruitment and neuropathic pain following peripheral nerve injury in rats. Eur J Neurosci 2007, 26: 3486–3500. 10.1111/j.1460-9568.2007.05971.x

Hu P, Bembrick AL, Keay KA, McLachlan EM: Immune cell involvement in dorsal root ganglia and spinal cord after chronic constriction or transection of the rat sciatic nerve. Brain Behav Immun 2007, 21: 599–616. 10.1016/j.bbi.2006.10.013