The link is not one to one, but there has to be significance to the immune response in central pain nerve injury. That we are not certain what sets off the inflammatory process, and whether it precedes or follows pain, does not change the fact it is there. Inflammation means acid around the neuron and acid means pain. The brain itself inherently feels no sensation, although the dura around it is susceptible to pain, but the same chemicals in a joint would cause severe joint pain. CP may be the expression of the inflammation.
See Moalem G and Tracey D J, Brain Res Brain Res Rev. 2005 Dec 30;
Neuropathic pain is characterized by “increased sensitivity to painful stimuli (hyperalgesia), the perception of innocuous stimuli as painful (allodynia) and spontaneous pain”. If the pain of light touch involves a delay of twenty seconds or so, as opposed to being instantaneous, you are talking about central pain. If light touch pain is instantaneous, you are speaking of peripheral nerve injury pain.
Immunology is a science unto itself. Thanks to the heavy duty research on AIDS, knowledge in this area changes so fast that only those directly involved can avoid the embarassment of appearing downright stupid in the whole area. Imagine the poor dermatologist who reads in his journal that if a nevus (mole) has a pale circle around it, (halo nevus) then the CD8+ T cells are destroying pigment, suggesting an immune reaction to a melanocytic lesion somewhere else in the body and necessitating perhaps a biopsy of the duodenum. This is all well and good, but what if the dermatologist hardly knows what a T cell is, let alone the C active variety, let alone the specific subtype of the CD8+ reaction in T cells against “moles”. In other words, immunology is complicated. It is not as complicated as pain, however, which goes further. This can work to your advantage if you find yourself facing a pain skeptic.
Who would have thought immunology had anything to do with pain, yet it does, neuropathic pain in particular. Roughly speaking, immune cells in the brain can be divided into two types (obviously many more, but bear with us). One type migrates into an inflammed area, drawn there by chemicals which call for them. In-moving cells include mast cells, neutrophils, macrophages and T lymphocytes The other type of immune cell is resident. It belongs right there in the brain. Resident immune type cells include microglia, and their action has recently been illuminated by Jeffrey Coull (see our article on the “Blockbuster Pain Article” in Nature).
As Moalem and Tracey inform us, “Neuropathic pain has been described in about 1% of the US population, is often severely debilitating and largely resistant to treatment. Animal models of peripheral neuropathic pain are now available in which the mechanisms underlying hyperalgesia and allodynia due to nerve injury or nerve inflammation can be analysed.” They fail to mention that the same is true of animal models of central pain. The “mechanical drop cord injury” (UTMB) model and the “erythrocin B sensitized laser injury of cord” model (Karolinska) both predictably render the animal an unwilling sufferer of central pain. This is true in primates as well as lab rats.
The immune response to nerve injury “leads to subsequent production and secretion of various inflammatory mediators. These mediators promote neuroimmune activation and can sensitise primary afferent neurones and contribute to pain hypersensitivity.”
Chemicals which are known to be inflammatory mediators are virtually all present in the dorsal root ganglia of those with Central Pain and in the thalamus. The question is, what is the hook up. Is the presence of immune cells primary or secondary. We really do not know yet, but knowing the neurons are inflammed (Our Australian friends will have it as “neurones”) gives more than enough evidence to any thoughtful, informed doctor that we are not kidding when we say the pain of central pain is severe. It may also help them to understand why opiates do not work, since opiates stimulate pain in the brain by inhibiting the pain inhibiting tracts (disinhibition).
It is difficult to get doctors to take central pain for the terror that it is. However, since they are intimidated by all the big immune talk of late, perhaps they will quit thinking they know all about pain and stop telling us it is “all in our head” if we ask them what action they feel the microglia are having when they block the action of GABA(A) by releasing BDNF and whether they think it has anything to do with the CD8+ action of T cells. You may not know what you are talking about either, but odds are it will save you a neuropsych evaluation if you ask this. Then you can get on with discussing your central pain with the dignity of being a real patient. This is worth a lot.
January 7th, 2006 at 9:32 am #julie
your articles are very helpful. from what you have read, do you think there could be an answer to the pain in the near future. it is so hard to make it through each minute.
Editor’s Note.
A straw poll from some at the site estimates 5-10 years.