Because we have previously published an article on SNSRs but there has been little follow up in the world’s research literature, it seemed worthwhile to revisit a segment on this topic. Any compound shown to be as potent as NMDA should certainly remain in conversation.
See May 24 2004 Proceedings of the National Academy of Science.
It continues to appear that the chemicals of pain and pain relief are kissing cousins. Grazzini et al , from Astra Zeneca have reported a previously undescribed group of G protein coupled receptors, the sensory neuron specific receptors, (SNSR) and even cloned them for research. SNSR is synthesized in the dorsal root ganglia (DRG) and spread to layers I and II of the cord, as well as to superficial terminals of nociceptor neurons (pain carrying neurons).
They found, amazingly, that fragments of a steroid related receptor protein, namely the C terminal end of gamma MSH or gamma 2 MSH stimulated SNSR-1 and produced thermal hyperalgesia and mechanical allodynia when applied to cord or dorsal root ganglia. The SNSR proteins are linked to the group of genes known as Mas genes. Making matters even MORE interesting was the discovery that BAM, a fragment of proenkephalin A also stimulates nociversive behavior, mechanical allodynia, and thermal hyperalgesia via SNSR3. Amazingly, SNSR is as potent at causing such pain as N-methyl-d-aspartate!. SNSR1 is effective at nano concentrations, ie nanomolar concentrations. BAM 8-22 and BAM 22 are both effective at causing neuropathic pain.
Why a proenkephalin should cause pain is a mystery. Consistent with the nonresponse of Central Pain to opioids, Grazzini also found that the opioid related compounds associated with SNSRs are operating through NONopioid pathways. An inconsistent result from opioids has been reported in the surveys of the Wall/McHenry database, highly suggestive that opiates may be helpful for
