Spinal leptin contributes to the pathogenesis of neuropathic pain in rodents
Grewo Lim, … , Yinghong Tian, Jianren Mao
Grewo Lim, … , Yinghong Tian, Jianren Mao
Published January 12, 2009
Citation Information: J Clin Invest. 2009;119(2):295-304. https://doi.org/10.1172/JCI36785.
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Research Article Neuroscience

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-1β 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

Grewo Lim, Shuxing Wang, Yi Zhang, Yinghong Tian, Jianren Mao

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Figure 5

Effect of leptin gene mutation on behavioral and cellular changes.

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Effect of exogenous leptin on behavioral and cellular changes. (A–D) Int...
Thermal hyperalgesia (A) and mechanical allodynia (C) on ipsilateral hind paw was prevented in ob/ob mice, as shown on days 1, 3, 5, and 7. ob/ob mice also showed a higher baseline nociceptive threshold to mechanical stimulation compared with wild-type mice (C and D). CCI did not change the thermal and mechanical nociceptive threshold on the contralateral hind paw of either ob/ob or wild-type mice (B and D). (E and F) ob/ob mice displayed a lack of leptin expression and a basal deficiency in Ob-Rb, JAK2, p-STAT3, NR1, and IL-1β expression within the spinal cord dorsal horn with no increase in expression on day 7 after CCI. Data are shown as mean ± SD. *P < 0.05 versus sham; #P < 0.05 versus ob/ob.