Pain sensitivity

Nociception pain perception can be measured in rodents by a variety of procedures whereby aversive stimulation is applied externally either by heat or electrical stimulation to the tail or paws (tail flick, hot plate, plantar test) or internally by injection into the peritoneum of chemicals (acetic acid, phenylbenzoquinone). Inflammation pain can also be induced by injecting chemicals (carrageenan, formalin) into the paws. More complex approaches induce neuropathic pain by surgical lesions, usually to the sciatic or spinal nerve. For safety pharmacology purposes, usually only the simpler procedures are used. For example, with the hot plate test [18] the animal is placed onto a heated metal plate (54°C) within a vertical cylinder, and the latency to licking its front paws is measured over a short period. 

---

Endogenous estrogens are known to be active in a number of areas of the brain. There are indications that estrogens may play a role in mood, locomotor activity, pain sensitivity, vulnerability to neurodegenerative diseases and cognition (McEwan, 1999). In humans, the blood brain barrier is not fiilly developed at birth and, for this reason, the central nervous system (CNS) may be more sensitive to phytoestrogens in utero or at birth. As ERs are expressed in the CNS, phytoestrogens may also be active in this area. 

Neuropathic pain is defined as spontaneous pain and hypersensitivity to pain associated with damage to or pathologic changes in the peripheral nervous system as in painful diabetic peripheral neuropathy (DPN), acquired immunodeficiency syndrome (AIDS), polyneuropathy, post-herpetic neuralgia (PHN) or pain originating in the central nervous system (CNS), that which occurs with spinal cord injury, multiple sclerosis, and stroke. Functional pain, a relatively newer concept, is pain sensitivity due to an abnormal processing or function of the central nervous system in response to normal stimuli. Several conditions considered to have this abnormal sensitivity or hyperresponsiveness include fibromyalgia and irritable bowel syndrome. 

Tenen, S. (1967). The effects of p-chlorophenylalanine, a serotonin depletor on avoidance adquisition, pain sensitivity and related behavior in the rat. Psychopharmacologia 10, 204-19. 

This material is hazardous by penetration through broken skin. Symptoms include sweating, salivation, vomiting, contractions, cramps, respiration is shallow and rapid, hypertension, rapid heart rate (tachycardia), and cardiac arrhythmia. May be mistaken for heart attack. Produces intense pain that becomes excruciating over time. Skin may be hyper pain sensitive. 

Features of central sensitization are pain in response to normally innocuous tactile stimuli, and the spread of pain sensitivity beyond the site of tissue injury. Central sensitization plays a major role in acute post-traumatic pain, and also in migraine, neuropathic pain (see below) and some diffuse chronic pain syndromes, such as fibromyalgia and irritable bowel syndrome. In these conditions, which have no detectable peripheral trigger, an autonomous central sensitization may be the pathology, increasing the gain in neuronal activity in the CNS and thereby producing abnormal responses to normal inputs. 

Peripheral inflammation increases prostanoid levels at the site of inflammation and this contributes directly to inflammation and peripheral sensitization (prostanoids and inflammation are discussed in Ch. 33). Peripheral inflammation also increases central prostanoid levels as a result of the central induction of COX-2, to mediate widespread changes in pain sensitivity as well as fever, anorexia, altered mood and sleep patterns [19]. 

Harvey, R. J. et al. GlyR alpha3 an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science 304 884-887, 2004. 

Like nitric oxide, the discovery of the eicosanoid signalling molecules was a significant event in twentieth century physiology, due largely to research led by Sir John Vane (Nobel Prize 1982). The diverse actions of the eicosanoids include roles in muscle contraction, blood coagulation, salt and fluid homeostasis, inflammatory responses and pain sensitivity. 

The subject of pain is a very complicated one on which we can touch only briefly, but the existence of a high degree of variability with respect to pain sensitiveness can hardly be questioned. 

Next in the scale of variation are numerous individuals who are subnormal in their pain sensitivity. Dr. Emanuel Libman found among his patients 30 to 40 per cent who belonged in this category. Dr. Leon J. Saul tested 97 pugilists and found only 10 who were significantly responsive to painful stimuli. 13... 

When pain thresholds are determined by other methods involving, for example, the application of measurable pressure to the calf of the leg, the range of variability is several-fold.17 No one method can be expected to give a complete picture of the pain thresholds, much less the more subtle matter of pain sensitivities. Presumably tests for the pain-inducing effect of heat applied to intestinal tissue of different individuals would yield uniformly negative results, but this, of course, does not mean that individuals are uniform in their pain sensitivity. 

Decreased pain sensitivity 3) Hyperreflexia with development of a Babinski sign (upward motion of the big toe following stimulation of the sole of the foot). 

Receptors for pressure, temperature, and pain. Sensitivity to the corresponding stimuli is enhanced. 

Headache is one of the most frequent complaints which mankind suffers from. Most commonly the headache starts from one of the pain sensitive structures of the skull, but diseases originating outside the skull are also important causes of headache. Diseases of the eye, sinuses, jaw, teeth and neck often cause headache, but also visceral tissue may give rise to headache. The headache may be secondary to many diseases, e.g. anaemia and hypertension. Drug induced headache is not uncommon, either as an adverse reaction, e.g. to calcium antagonists and SSRIs, or as part of more complex problems in chronic headache. 

PGE2 Vasodilation, decreased gastric acid secretion, pain sensitization, nterine contraction, cervical ripening, maintenance of patent dnctns arteriosns, bronchodilation, fever... 

Increased levels of progesterone are known to be associated with decreases in pain sensitivity (G. A. Frye et al. 1993 Gintzler and Bohan 1990], but the mechanisms by which progesterone exerts its antinoceptive effects are unclear. A first description of analgesic properties of neurosteroids, for example. 

Frisoni GB, De Leo D, Rozzini R, et al Psychic correlates of sleep symptoms in the elderly. Int J Geriatr Psychiatry 7 891-898, 1992 Fritschy J, Benke D, Mertens S, et al 5 types of type A GABA receptors identified in neurons by double and triple immunofluorescence staining with subunit specific antibodies. Proc Natl Acad Sci USA 89 6726-6730, 1992 Frye CA, Duncan JE Progesterone metabolites effective at the GABAa receptor complex attenuate pain sensitivity in rats. Brain Res 643 194-203, 1994 Erye CA, Cuevas CA, Crystal S, et al Diet and estrous cycle influence pain sensitivity in rats. Pharmacol Biochem Behav 45 255-260, 1993 Erye PE, Arnold LE Persistent amphetamine-induced compulsive rituals response to pyridoxine (B6). Biol Psychiatry 16 583-587, 1981... 

EP1 receptor knock-out mice show reduced pain sensitivity, suggesting an important role for this receptor subtype in pain perception (Stock et al., 2001). Furthermore these mice show a significant reduction in systolic blood pressure and an increased renin angiotensin activity, suggesting a role also in cardiovascular homeostasis. 

This test, performed in rats, is the classical model of inflammatory pain. Intraplantar injection of inflammatory stimuli such as carrageenan, kaolin, or complete Freund adjuvants (CFA) induces paw swelling and increased pain sensitivity. As pain stimulus pressure is applied on the inflammed paw and gradually increased until the animal responds by vocalisation or withdrawal of the paw. Analgesics increase the pressure threshold (Randall and Selitto, Arch. Int. Pharmacodyn. 1957, 111, 409-419). 

Pain Sensitivity This side effect causes the pain of injuries to be intensified for the user of the drag the more intense the pain, the more debilitating the effects. For every 5 points of damage the user suffers, he suffers ld3 points of nonlethal damage as well. 

---