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Query: UMLS:C0344307 (
analgesia
)
28,200
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Analgesic tolerance to opioids contributes to the opioid crisis by increasing the quantity of opioids prescribed and consumed. Thus, there is a need to develop non-opioid-based pain-relieving regimens as well as strategies to circumvent opioid tolerance. Previously, we revealed a non-opioid analgesic mechanism induced by median nerve electrostimulation at the overlaying PC6 (Neiguan) acupoint (
MNS
-PC6). Here, we further examined the efficacy of
MNS
-PC6 in morphine-tolerant mice with neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Daily treatments of
MNS
-PC6 (2 Hz, 2 mA), but not electrostimulation at a nonmedian nerve-innervated location, for a week post-CCI induction significantly suppressed established mechanical allodynia in CCI-mice in an orexin-1 (OX
1
) and cannabinoid-1 (CB
1
) receptor-dependent fashion. This antiallodynic effect induced by repeated
MNS
-PC6 was comparable to that induced by repeated gabapentin (50 mg/kg, i.p.) or single morphine (10 mg/kg, i.p.) treatments, but without tolerance, unlike repeated morphine-induced
analgesia
. Furthermore, single and repeated
MNS
-PC6 treatments remained fully effective in morphine-tolerant CCI-mice, also in an OX
1
and CB
1
receptor-dependent fashion. In CCI-mice receiving escalating doses of morphine for 21 days (10, 20 and 50 mg/kg), single and repeated
MNS
-PC6 treatments remained fully effective. Therefore, repeated
MNS
-PC6 treatments induce
analgesia
without tolerance, and retain efficacy in opioid-tolerant mice via a mechanism that involves OX
1
and CB
1
receptors. This study suggests that
MNS
-PC6 is an alternative pain management strategy that maybe useful for combatting the opioid epidemic, and opioid-tolerant patients receiving palliative care. PERSPECTIVES: Median nerve stimulation relieves neuropathic pain in mice without tolerance and retains efficacy even in mice with analgesic tolerance to escalating doses of morphine, via an opioid-independent, orexin-endocannabinoid-mediated mechanism. This study provides a proof of concept for utilizing peripheral nerve stimulating devices for pain management in opioid-tolerant patients.
...
PMID:Median Nerve Stimulation as a Nonpharmacological Approach to Bypass Analgesic Tolerance to Morphine: A Proof-of-Concept Study in Mice. 3306 69
