More and more, the difference between regular (nociceptive) and nerve injury pain (neuropathic) refuses to declare itself. The same chemicals seem to operate in both spheres. The primary difference is in the chronicity. The growth factors from glia take over the genes of the neuron and force it to make pain exciters, and KEEP ON MAKING THEM.
Ever since Tarek Samad with Woolf’s group at Harvard showed that neuropathic pain is marked by cytokines in the thalamus, we have known that acids went all the way up the pain transmission chain.
Recently, Samad’s work was corroborated by Fu et al in Neurochem Res. 2006 Mar;31(3):333-40 These researchers showed that interleukin 1 beta is produced in neurons, but NOT in glia, after a surgical incision. However, the increase in IL1b, which for all intents and purposes can be thought of as an acid causing cytokine, was TEMPORARY.
Since the same pain chemicals are found in both nociceptive and neuropathic pain, we simply must learn more about WHY the genes refuse to quit making interleukin 1b in central pain. IL1b is sure to cause acid to be manufactured, and can be thought of as equivalent to acid.
Of course, in nerve injury the nerves remain injured, so inflammation could be expected to continue. We need to understand the signal for acids to be released as part of pain, and then find out why that signal never stops in central pain. Transcription of the pain exciters keeps on coming and coming like the Eveready bunny. Although IL1b is happening in neurons but not glia, there is little doubt that the signal for the neurons DOES originate with glia, which set off inflammation. Or, perhaps, the glia merely maintain the signal and something ELSE sets it off. If so, what is that signal?
Post-surgical pain is a warning, an alert, a normal response to injury. Pain is part of the physiologic functioning of the pain apparatus. Without it, we might jump up from surgery and rip out the stitches. It is disspiriting however, that it is unknown how a cut in the skin makes for IL1b in the spinal cord. It is time to get serious about pain signalling, what turns it on, and what turns it off.
The central pains are divergent in the nature of their perception from normal pain. Normal pain has great participation from the big, accurate, fast pain fibers, the A betas. However, C fibers, which probably drive central pain are poorly localized and capable of recruiting firing in neighbor neurons without enough specificity to recognize and sort out what types of pain are going on. The result is the protopathic burning which we call dysesthesia. Why is there greater participation of C fibers in chronic pain? What is the signal behind this?
We do know that nerve injury pain requires some sort of circulatory compromise, initially at least, some ischemia or interruption of blood flow. Is there something lingering in the nerve to make it think it still has poor circulation? Put a blood pressure cuff around your arm, very tight, and then squeeze a rubber ball. Very soon, the normal person will feel protopathic burning. The discriminating part of the pain nerve has been disabled by poor circulation. When there is no capsaicin handy, this is one good way to satisfy skeptics that your pain is real, provided you have a blood pressure cuff and a rubber ball. Just say if you will explain why a nerve deprived of oxygen can hurt, I will explain to you why a mashed or injured nerve can initiate pain firing.
Something forces the nerve to continue to send out protopathic burning signal in CP, even when circulatory compromise has ended every other sensation from the nerve. It seems important to pin down this easily demonstrated phenomenon. If Fu is correct, that signal manifests early on by kicking out the interleukin 1 beta, but how does that message get to the cord, what is the chemical signal? It is fine to say the definitive signal is cytokines like IL1b, but WHAT cranks them up, what starts the show? In central pain, the initial starting up plays over and over again, like a stuck record. Is there no scientist who can time the thing carefully enough to see what is linked to the beginning?