title: Limited BDNF contributes to the failure of injury to skin afferents to produce a neuropathic pain condition.
abstract: Although a large body of evidence has shown that peripheral nerve injury usually induces neuropathic pain, there are also clinical studies demonstrating that injury of the sural nerve, which almost only innervates skin, fails to do so. The underlying mechanism, however, is largely unknown. In the present work, we found that the transection of either the gastrocnemius-soleus (GS) nerve innervating skeletal muscle or tibial nerve supplying both muscle and skin, but not of the sural nerve produced a lasting mechanical allodynia and thermal hyperalgesia in adult rats. High-frequency stimulation (HFS) or injury of either the tibial nerve or the GS nerve induced late-phase long-term potentiation (L-LTP) of C-fiber-evoked field potentials in spinal dorsal horn, while HFS or injury of the sural nerve only induced early-phase LTP (E-LTP). Furthermore, HFS of the tibial nerve induced L-LTP of C-fiber responses evoked by the stimulation of the sural nerve and the heterotopic L-LTP was completely prevented by spinal application of TrkB-Fc (a BDNF scavenger). Spinal application of low dose BDNF (10pg/ml) enabled HFS of the sural nerve to produce homotopic L-LTP. Finally, we found that injury of the GS nerve but not that of the sural nerve up-regulated BDNF in DRG neurons, and that the up-regulation of BDNF occurred not only in injured neurons but also in many uninjured ones. Therefore, the sural nerve injury failing to produce neuropathic pain may be due to the nerve containing insufficient BDNF under both physiological and pathological conditions.
authors: Pain Research Center and Department of Physiology, Zhongshan Medicine School of Sun Yat-Sen University, 510089 Guangzhou, China Department of Anesthesia, The Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510120, China Department of Anatomy, Zhongshan Medicine School of Sun Yat-Sen University, 510080 Guangzhou, China.
authors: Li-Jun
authors: LJ
authors: Zhou
authors: Wen-Jie
authors: WJ
authors: Ren
authors: Yi
authors: Y
authors: Zhong
authors: Tao
authors: T
authors: Yang
authors: Xu-Hong
authors: XH
authors: Wei
authors: Wen-Jun
authors: WJ
authors: Xin
authors: Cui-Cui
authors: CC
authors: Liu
authors: Li-Hua
authors: LH
authors: Zhou
authors: Yong-Yong
authors: YY
authors: Li
authors: Xian-Guo
authors: XG
authors: Liu
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000145:classification / Q000503:physiopathology; D007136:Immunoglobulins / Q000494:pharmacology; D037102:Lectins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D051474:Neuralgia, Postherpetic / Q000473:pathology* / Q000503:physiopathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D017288:Pain Threshold / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000276:immunology; D012867:Skin / Q000294:innervation*; D018709:Statistics, Nonparametric; D013266:Stilbamidines; D013497:Sural Nerve / Q000378:metabolism / Q000503:physiopathology; D013979:Tibial Nerve / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D007136:Immunoglobulins; D037102:Lectins; D016900:Neurofilament Proteins; D013266:Stilbamidines; C051774:neurofilament protein H; D020813:Receptor, trkB