Dr. Bryan Hains had the most signficant paper presented at the recent annual meeting of the American Pain Society.
At the recent scientific gathering of pain specialists, the usual institutions were well represented, with the addition of the University of Colorado, which reported that opiates actually increase glial activation.
Readers at this site have long been aware that reactive oxygen species are important in pain. They also are aware that activation and growth in number of the glia which surround neurons in the cord are involved in hypersensitization. This information, although actually unproven to be THE complete cause of neuropathic pain, is so pervasive that it is hard to imagine a mechanism which is not at least footed on neuroinflammation coming from glial activation. Dozens of articles at painonline have been directed at these concepts. The presenters from UTMB emphasized the role of GABA-A in neurons running against the normal pathways to the brain, what is called antidromic neurotransmission. This was also interesting.
However, the real showstopper, as far as this author was concerned, was the paper by Dr. Bryan Hains from Yale. You will recall that it was Hains who discovered that Nav 1.3, a FETAL ion channel (manufactured by alterations in gene regulation caused by nerve injury) is the sodium channel in central pain as opposed to Nav 1.8 which is the normal sodium channel in pain neurons. Nav 1.8 does not participate in central pain.
Dr. Hains suggested that after spinal cord injury microglial activation causes an increase in neuropathic pain and lowered thresholds for nociceptive (normal) pain. This means glial activation participates in both DYSESTHESIA and HYPERPATHIA. His real contribution however was the revelation that blocking cysteine-cysteine chemokine ligand 21, a gene associated with immune behavior and neuroinflammation, reduces activation of microglia and also reduces hyperexcitability by restoring normal nociceptive thresholds. Here then is a hopeful direction for therapeutic agents, something to promote cysteine-cysteine chemokine ligand 21.
Although Dr. Hains is at Yale, he was trained at UTMB. Dr. Carl Saab, at Brown, one of the authors here, also trained with Dr. Hains at UTMB. We have much to be grateful for to Wm Willis Jr, who continues to turn out the very best in pain researchers. Likewise, the fine professors at UCSD, Harvard, NIH, UCSF, and Univ. of Washington are doing more than their share of pain research. Like football teams, things seem to vary from year to year, but there are consistent performers. Generally you will find leaders with faculty from the institutions mentioned. Being human, we probably do not show sufficient gratitude for these hardworking scientists. If there is more charitable work in the world, we do not know about it.
“Nociceptive” pain is another word for normal pain, as opposed to nerve injury pain, which is termed “neuropathic” pain. Nociception comes from the same root as the word “noxious”.
Glia, or which microglia are the most common around pain neurons, as cells linked to the immune process. They manufacture growth factors which lead to transcription factors, which modify gene output. The usual signal for glial activation is TNF alpha. However, you must read the preceding articles at this site to understand that somewhat complicated process. The bottom line is glial signalled production of preproinflammatory molecules by the genes, which lead to glial activation and hypersensitization, or in other words, central pain.