This is a joke: we would never try to prove Melzack & Wall wrong. That being said, MOGILab believes that science is better advanced by pointing out flaws or limitations in existing theories rather than providing more evidence for them. Thus, we are always on the lookout for data that challenge the status quo in the pain field. A few examples of this are provided here.
Conditioned Pain Modulation
The phenomenon currently known as “conditioned pain modulation” (CPM), “diffuse noxious inhibitory controls” (DNIC), “descending control of nociception” (DCN), or simply “counterirritation” relies on the observation that pain in one part of the body inhibits pain in another part. This phenomenon has been shown electrophysiologically, and behaviourally in both rodents and humans. MOGILab recently documented that, in both mice and rats, this is only true when the “test” stimulus (i.e., the noxious stimulus being measured before and during/after application of the “conditioning” stimulus) is of high intensity. When using (currently far more common) lower-intensity test stimuli, instead of analgesia we see robust hyperalgesia. In studies designed to evaluate the neurochemistry of this “anti-CPM”, we have shown that like CPM (but in the opposite direction), a2-adrenergic receptors and 5-HT7 serotonin receptors are required.
The “Purpose” of Chronic Pain
Many lectures on pain start (after going over the definition of pain itself) with a reflection on the evolutionary purpose of pain. Acute pain (seconds to minutes) is thought to be important for the avoidance or minimization of injury, and also as a robust teaching signal. Tonic pain (hours to days) is thought to be important as a mechanism to enforce recuperation, so that healing is promoted. But what about chronic pain? Chronic pain is said to have no adaptive value whatsoever; it’s a pathology, like “a smoke alarm stuck in the ON position even though there is no longer a fire.” But is this true? A study by Robyn Crook and colleagues (Curr. Biol., 24:1121-1125, 2014) performed in squid (!) showed that the nociceptive sensitization that accompanies chronic pain states reduces predation risk, and thus the “purpose” of chronic pain might be to enhance vigilance to predation. MOGILab designed a maze task to test this prediction in mice, and showed that neuropathic pain does indeed make mice hypervigilant to predator odours.
Why Poor Translation in Pain?
MOGILab has long been acutely interested in why analgesic drug development has such a poor translation record. Most have placed the blame on preclinical models (see Animal Models), and although it is certainly true that these models remain suboptimal, other factors may well be involved. We conducted a meta-analysis of published clinical trials of drugs for neuropathic pain, and discovered that responses in the placebo arm of those trials were increasing over time, whereas responses in the drug arm were not. Of great interest is the fact that this trend was much more pronounced in clinical trials conducted in the United States versus elsewhere. Thus, poor translation in the pain field may have as much to do with changes in clinical trial environments as poor preclinical practices.