title: Spinal leptin contributes to the pathogenesis of neuropathic pain in rodents.
abstract: Pain after nerve injury, a phenomenon referred to as neuropathic pain, is a debilitating clinical condition, but the underlying mechanisms remain unclear. As leptin, an adipocytokine produced mainly by nonneuronal tissue, has been implicated in the regulation of neuronal functions, we examined the role of leptin in neuropathic pain using a rat model of the condition chronic constriction sciatic nerve injury (CCI). We report that leptin critically contributed to pain behaviors following CCI. Specifically, spinal administration of a leptin antagonist prevented and reversed neuropathic pain behaviors in rats. Further examination revealed that levels of both leptin and the long form of the leptin receptor (Ob-Rb) were substantially increased within the ipsilateral spinal cord dorsal horn after peripheral nerve injury. Mechanistic studies showed that leptin upregulated the expression of both the spinal NMDA receptor and IL-1beta through the JAK/STAT pathway. Furthermore, these CCI-induced behavioral and cellular responses were diminished in leptin-deficient mice and mimicked by spinal administration of exogenous leptin in naive rats. Our findings reveal a critical role for spinal leptin in the pathogenesis of neuropathic pain and suggest what we believe to be a novel form of nonneuronal and neuronal interactions in the mechanisms of pathological pain.
authors.affiliation: MGH Center for Translational Pain Research, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Grewo
authors.initials: G
authors.lastname: Lim
authors.forename: Shuxing
authors.initials: S
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Tian
authors.forename: Jianren
authors.initials: J
authors.lastname: Mao
mesh_terms: D000818:Animals; D053583:Interleukin-1beta / Q000032:analysis; D053614:Janus Kinase 2 / Q000502:physiology; D020738:Leptin / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000209:etiology*; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*
chemical_list: D053583:Interleukin-1beta; D020738:Leptin; C409466:NR1 NMDA receptor; D054411:Receptors, Leptin; D016194:Receptors, N-Methyl-D-Aspartate; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2