Targeting neuroinflammation in neuropathic pain and opioid use.
Han-Rong WengTimothy M DoylePublished in: The Journal of experimental medicine (2022)
Neuropathic pain arises from injuries to the nervous system. It affects 20% of the adult US population and poses a major socioeconomic burden yet remains exceedingly difficult to treat. Current therapeutic approaches have limited efficacy and a large side effect profile that impedes their ability to treat neuropathic pain effectively. Preclinical research over the last 30 yr has established the critical role that pro-inflammatory neuro-immune cell interactions have in the development and maintenance of neuropathic pain arising from various etiologies. Pro-inflammatory neuro-immune cell interactions also underlie the development of adverse side effects of opioids and the loss of their efficacy to treat pain. Evidence from work in our lab and others in preclinical animal models have shown that signaling from the bioactive sphingolipid, sphingosine-1-phosphate (S1P), through the S1P receptor subtype 1 (S1PR1) modulates neuro-immune cell interactions. Here, we discuss how targeting S1P/S1PR1 signaling with S1PR1 antagonists already Food and Drug Administration-approved or in clinical trials for multiple sclerosis can provide a viable pharmacotherapeutic approach to reduce neuro-immune cell inflammatory signaling and potentially treat patients suffering neuropathic pain and the adverse effects of opioids.
Keyphrases
- neuropathic pain
- spinal cord
- spinal cord injury
- multiple sclerosis
- drug administration
- clinical trial
- chronic pain
- end stage renal disease
- pain management
- ejection fraction
- chronic kidney disease
- traumatic brain injury
- newly diagnosed
- randomized controlled trial
- cell therapy
- oxidative stress
- prognostic factors
- peritoneal dialysis
- stem cells
- patient reported outcomes
- emergency department
- lipopolysaccharide induced
- inflammatory response
- climate change
- brain injury
- cognitive impairment
- phase ii
- patient reported