NSAID/arthritis pills have painkilling action centrally and this now appears to be related to its effect on opioid system. Unfortunately it means you can develop tolerance either because you are on an opioid or because its effects on descending inhibitory circuits do undergo tolerance.
Tsiklauri, Nana, et al.
Antinociceptive tolerance to NSAIDs in the anterior cingulate cortex is mediated via endogenous opioid mechanism.
BMC Pharmacology and Toxicology 19.1 (2018): 2.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756434/pdf/40360_2017_Article_193.pdf
- ACC is the area where emotional representation of pain registers -lesioning there eliminates emotional pain representation but not the physical – so it is the “unpleasantness” centre
- “repeated administration of NSAIDs systemically or in the midbrain periaqueductal grey matter (PAG) induced tolerance to these drugs, similarly to opioid analgesics, and cross-tolerance to morphine”
- research findings have “strongly support the suggestion of endogenous opioids involvement in NSAIDs antinociception and tolerance in the descending pain-control system”
- NSAID action on ACC can be blocked by naloxone confirming NSAID brain effects are through opioid system.
- morphine tolerant rats are also NSAID tolerant suggesting both mediated through opioid system
- “anti-nociception induced by systemic metamizol [an NSAID] involves endogenous opioids that can be blocked by naloxone at the levels of the PAG, the NRM and the spinal dorsal horn [32], as well as other findings that endogenous opioids are involved in the potentiation of analgesia observed with a combination of morphine plus dipyrone [33]. These data suggest a role for endogenous opioidergic descending pain control circuits.”
Comment – if subject tolerant to opioids, then adding an NSAID might not help. Subjects that have a poor descending inhibitory circuits (FM, migraines, IBS) might do poorly on NSAID’s and opioids.