Journal article
Tumor necrosis factor receptor 1 inhibition is therapeutic for neuropathic pain in males but not in females
Pain (Amsterdam), v 160(4), pp 922-931
01 Apr 2019
PMID: 30586024
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Tumor necrosis factor (TNF) is a proinflammatory cytokine, which is involved in physiological and pathological processes and has been found to be crucial for pain development. In the current study, we were interested in the effects of blocking Tumor necrosis factor receptor 1 (TNFR1) signaling on neuropathic pain after peripheral nerve injury with the use of transgenic mice and pharmacological inhibition. We have previously shown that TNFR12/2 mice failed to develop neuropathic pain and depressive symptoms after chronic constriction injury (CCI). To investigate the therapeutic effects of inhibiting TNFR1 signaling after injury, we delivered a drug that inactivates soluble TNF (XPro1595). Inhibition of solTNF signaling resulted in an accelerated recovery from neuropathic pain in males, but not in females. To begin exploring a mechanism, we investigated changes in N-methyl-D-aspartate (NMDA) receptors because neuropathic pain has been shown to invoke an increase in glutamatergic signaling. In male mice, XPro1595 treatment reduces elevated NMDA receptor levels in the brain after injury, whereas in female mice, NMDA receptor levels decrease after CCI. We further show that estrogen inhibits the therapeutic response of XPro1595 in females. Our results suggest that TNFR1 signaling plays an essential role in pain induction after CCI in males but not in females.
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Details
- Title
- Tumor necrosis factor receptor 1 inhibition is therapeutic for neuropathic pain in males but not in females
- Creators
- Tania del Rivero - Drexel UniversityRoman Fischer - Drexel Univ, Dept Biol, 3245 Chestnut St, Philadelphia, PA 19104 USAFan Yang - Drexel Univ, Dept Biol, 3245 Chestnut St, Philadelphia, PA 19104 USAKathryn A. Swanson - Drexel Univ, Dept Biol, 3245 Chestnut St, Philadelphia, PA 19104 USAJohn R. Bethea - Drexel University
- Publication Details
- Pain (Amsterdam), v 160(4), pp 922-931
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 10
- Grant note
- Drexel DARE (Drexel Area of Research Excellence) FI 2138/1-1 / DFG research fellowship; German Research Foundation (DFG)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; Neurobiology and Anatomy
- Web of Science ID
- WOS:000480759700016
- Scopus ID
- 2-s2.0-85063255175
- Other Identifier
- 991019169507704721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Anesthesiology
- Clinical Neurology
- Neurosciences