"Noxious stimuli and responses
There are three categories of noxious stimuli:
- mechanical (pressure, swelling, abscess, incision, tumour growth);
- thermal (burn, scald);
- chemical (excitatory neurotransmitter, toxic substance, ischaemia, infection).
- substance P;
"Endometriotic implants cause a local inflammatory reaction which irritates nerve endings and sends noxious stimuli along the nerve pathways to the spinal cord and into the central nervous system (CNS) where they are interpreted as burning, dull, achy sensations or as sharp, stabbing, or crampy pains. The local inflammatory reaction is mediated by the increased production of substances, such as a variety of cytokines and prostaglandins, originating from the endometriotic implants and cells of the immune system. These substances also stimulate development of scarring and nodules around the endometriotic implants which may compress peripheral nerves compounding pain symptoms with signs of peripheral neuropathy. Pain symptoms are usually elicited when the nodules are compressed during pelvic examination or sexual intercourse. Endometriotic (chocolate) cysts may compress on other pelvic organs, causing pain and pressure during urination or bowel movements. If there is bleeding from the endometriotic lesions, as it frequently happens during the menstrual period, a woman may notice blood in the urine or stools or in secretions from other organs affected by endometriosis, e.g. blood in the sputum with endometriosis of the lungs. Because of increased systemic cytokine and prostaglandin production by the circulating immune cells, some women with endometriosis may experience generalized symptoms such as low-grade fever; crampy, generalized aches and pains; and nausea, vomiting, and diarrhea usually around the time of the menstrual period." http://www.endometriosisinstitute.com/endometriosis/management-of-pelvic-pain
"Calcium-binding proteins seem to be increased in endometriosis-associated nerve fibres and might play an important role in the chronic inflammatory condition and the pain pathogenesis of endometriosis." http://onlinelibrary.wiley.com/doi/10.1002/j.1532-2149.2013.00323.x/abstract;jsessionid=A4A598F96BBAA715C3121D4E3C8056D0.f02t02?deniedAccessCustomisedMessage=&userIsAuthenticated=false
"While increased levels of leptin have been reported in patients with endometriosis, their contribution to endometriosis pain has not been explored. Using a rodent model of endometriosis we provide evidence for an estrogen-dependent contribution of leptin in endometriosis-induced pain....This sensitivity to leptin is dependent on estrogen levels." http://www.sciencedirect.com/science/article/pii/S0306452213009482
"The exact aetiology of endometriosis is still not clear although a role for inflammation is increasingly accepted. We therefore investigated the inflammatory activity of eutopic tissue and that of the matching ectopic lesions from different locations by measuring the genetic expression of inflammatory chemokines and cytokines. The gene expression in matching eutopic and ectopic tissue was compared, as was the gene expression in lesions from different locations. A significantly higher mRNA expression of the chemokines ENA-78 and RANTES and the cytokines IL-6 and TNFα was observed in endometriotic lesions of the rectovaginal septum (RVS) compared to that of matching eutopic tissue. Comparisons across lesion locations showed a significantly higher expression of IL-6 and TNFα in the RVS compared to lesions from either the ovaries or the peritoneum. These results show that the production of some inflammatory chemokines and cytokines is significantly increased in the ectopic endometrial tissue compared to matching eutopic tissue. Furthermore, IL-6 and TNFα are produced in significantly higher quantities in RVS lesions compared to other lesions." http://www.hindawi.com/journals/mi/2013/450950/abs/
"Based on research, the best understanding we now have is that migraine arises from abnormally excitable neurons in the brain and trigeminal nerve. What causes the neurons to be abnormally excitable? Various things can do this, including low magnesium, abnormal calcium channels on the surface of the neuron, mitochondrial abnormalities, or other inherited brain chemical abnormalities. The newest things in the migraine story are the glia—the support cells in the brain—which also appear to have a role in transmitting pain, perhaps more so in chronic headache, although their story is still being determined....While there is still some controversy over the "vascular" part of migraine, the situation was recently summed up by Dr. Andrew Charles, UCLA migraine researcher. Dr. Charles indicated that while it is clear that vascular changes occur in migraine, it does not mean migraine is triggered by vascular processes, and that the dilation of blood vessels is neither necessary nor sufficient for causing migraine pain.
"According to existing trigeminovascular theory, once the messages come from the activated cells in the trigeminal nucleus in the brainstem, and travel to the trigeminal nerves that go to the dural blood vessels on the brain's surface, it causes dilation. However, the trigeminal activation also causes the release of brain chemicals called neuropeptides (substance P, CGRP or calcitonin gene-related peptide, neurokinin A, 5HT or serotonin, and noradrenalin).
"The release of these chemicals causes inflammation, and what is called peripheral sensitization. This is most likely what results in the throbbing pain most people experience. As the attack progresses, something can occur called central sensitization. When this occurs, it causes what is known as cutaneous allodynia. This means that things that are usually just a normal touch are now felt as painful. Many headache patients with allodynia cannot continue to wear earrings, necklaces or neckties, or their glasses. Some find that they cannot lie down on the side of the head pain, or report that "even their hair hurts." Up to 80% of migraine sufferers are affected by some degree of cutaneous allodynia, and it generally occurs in the late stages of a migraine attack when the pain is severe. This is why it is important to treat early when the pain is mild or moderate.
"When central sensitization becomes advanced, it can involve areas beyond the head, and simple touch on the arms or shoulder can be perceived as painful. For example, I am aware of one migraine sufferer who is bothered by the seams in her clothing during such an attack. At this stage of the migraine, migraine-specific medication is less likely to be helpful, and studies have shown that while they will reduce the pain and relieve the throbbing, they cannot abort the attack, and allodynic pain remains as well as other migraine symptoms. In late-stage migraine, other medications may be necessary in order to end the attack." http://www.migrainesurvival.com/understand-migraine-pathophysiology-allodynia