Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reported evidence indicates that the dorsal region of the periaqueductal gray matter (PAG) is involved in the modulation of both pain and aversion, and that opioid mechanisms, among others, participate in their modulation. Since many central actions of bradykinin (BK) have been shown to be similar to those of morphine, the present was undertaken to measure the effects of microinjection of BK into the PAG on the thresholds of aversive electrical stimulation of the same brain area and of dental pulp electrical stimulation. Bradykinin, injected into the dorsal PAG, induced a dose-dependent increase in the aversive threshold, an effect similar to that reported by others for morphine. Also, as reported for morphine, the antiaversive effect of BK was antagonized by naloxone injected intraperitoneally. Whereas subcutaneously administered morphine induced marked analgesia, intra-PAG administration of BK caused a small but significant hyperalgesia. Similarly, morphine injected into the dorsal PAG tended to cause hyperalgesia instead of analgesia. Furthermore, the hyperalgesic effect of BK also appears to involve opioid mechanisms since it was blocked by naloxone. As in previously reported studies, intracerebroventricularly injected BK raised the pain threshold. These results indicate that BK mobilizes opioid mechanisms in the dorsal PAG that inhibit aversion but not pain.
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PMID:Opioid mediation of the antiaversive and hyperalgesic actions of bradykinin injected into the dorsal periaqueductal gray of the rat. 140 99

A method for assessing inflammatory pain response was developed by modification of the formalin test. Formalin (0.5%, 25 microliters) was injected into the hindpaw of the mouse, and the durations spent in licking or biting response were measured as an indicator of pain response. The response curve was biphasic, having two peaks, from 0 to 5 min (first phase) and from 15 to 20 min (second phase). Morphine, ethylketocyclazocine, ketocyclazocine and pentazocine inhibited the response dose-dependently at the first and the second phases. Aspirin, oxyphenbutazone and dexamethasone inhibited only the second phase. Aminopyrine and mefenamic acid which acted at both central and peripheral sites inhibited both phases; however, the inhibition of the second phase was stronger than that of the first phase. Substance P (SP) antagonist inhibited only the first phase. Bradykinin (BK) inhibitor caused a inhibition of both first and second phases, and pretreatment of compound 48/80 and indomethacin inhibited only the second phase. From these facts, it was suggested that SP and BK played a role in the pain response at the first phase, and histamine, BK and PG were involved at the second phase. Naloxone produced hyperalgesia and bestatin produced analgesia at the second phase; then, it seems that the endogenous opioid system is activated by formalin stimulation and modulates the pain perception. Based on these findings, it is presumed that the pain of the first phase is evoked by the direct stimulation of the nerve fibers, and that of the second phase is due to the inflammatory reaction.
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PMID:[Studies of inflammatory pain response: related pain producing substance and endogenous opioid system]. 372 60

Polypeptides are endogenous agents, involved in the regulation of many physiologic functions and the pathogenesis of several diseases. Polypeptide antagonists form a group of new chemical entities which may provide valid therapeutic agents. Some polypeptides (angiotensin, kinins) are released through the action of proteolytic enzymes (renin, kallikreins) and act as hormones or autacoids; others (substance P, neurotensin) are synthetized by nervous cells to serve as neurotransmitters or neuromodulators. The main homeostatic role of the renin-angiotensin system is to uphold high systemic arterial blood pressure. Overproduction of renin and insufficient checking of renin secretion are among the most common causes of arterial hypertension. Several forms of arterial hypertension (neurovascular, idiopathic) benefit from a reduction in renin-angiotensin system activity. This is achieved either through decreasing renin secretion, by inhibiting conversion of angiotensin I into angiotensin II, or through blocking the peripheral actions (at the receptor sites) of angiotensin II. Renin secretion is very significantly reduced by beta-blocking agents (propranolol); conversion of angiotensin I into angiotensin II is inhibited by teprotide, captopril and their derivatives; peripheral actions of angiotensin II are blocked by saralasin. Bradykinin and related agents produce vasodilation, increase vascular permeability and stimulate pain fibers. Kinins thus reproduce the cardinal features of inflammation and are held to be mediators of the inflammatory reaction. The substance P neuropeptide is found in the brain and bowel; it may act as a transmitter of the sensation of pain at the spinal cord and central nervous system sites. Among other effects outside of the brain, substance P is a potent vasodilator and inhibits renin secretion. Neurotensin is a neuropeptide which produces hypothermia, muscular relaxation and analgesia. Outside of the brain, this peptide is involved in the regulation of gastric secretion, intestinal motility and insulin and glucagon secretion. The vasoactive intestinal peptide, found in certain cholinergic nerve endings, is a large peptide which inhibits gastric secretion, intestinal motility and vascular tone.
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PMID:[Polypeptides and antagonists]. 620 6

Cats were used to assess the significance of differences in animal preparations in the study of anesthetic-induced analgesia. Comparison was made between pentobarbital-anesthetized and decerebrate non-anesthetized cats. Bradykinin dissolved in normal saline was injected into the femoral artery as a noxious stimulus, and the neural response in the spinal cord lateral funiculus was recorded using the multi-unit activity technique. The magnitude of the neural response and the changes in spontaneous firing were compared before and after cervical cord transection at C1. Before the transection, the response was greater in anesthetized than in decerebrate cats. The cord transection potentiated the response in both preparations, but the degree of potentiation was greater in decerebrate than in anesthetized cats. These studies confirmed the presence of a descending pain inhibition system acting tonically on the nociceptive neural mechanisms in the spinal cord, and indicated the susceptibility of this system to pentobarbital. We conclude that pretreatment with pentobarbital induces pharmacologically a state of partial spinal cord transection and reduces the effects of drugs acting through supraspinal CNS structures.
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PMID:Pentobarbital-anesthetized and decerebrate cats reveal different neurological responses in anesthetic-induced analgesia. 731 83

The i.c.v. administration of bradykinin (4, 8 and 16 micrograms) induced antinociception in mice which was resistant to naloxone; furthermore, the induction of tolerance to morphine by a single s.c. injection (100 mg/kg, 24 h before test doses of the peptide) did not affect antinociception. Since bradykinin is known to increase nitric oxide (NO) in peripheral tissues, we studied the possibility that its antinociceptive action may be related to NO effects in the central nervous system. Bradykinin effects were antagonized by previous treatment with NG-nitro-L-arginine or concomitant i.c.v. administration of bradykinin and methylene blue. The immediate precursor of NO, L-arginine, which by itself produces analgesia, also reduced bradykinin effects; moreover, tolerance to L-arginine significantly decreased the response to the peptide. These results suggest that NO is involved in antinociception induced by i.c.v. administration of bradykinin.
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PMID:Possible role of nitric oxide in the antinociceptive action of intraventricular bradykinin in mice. 888 7

Bradykinin (BK) given into the plantar (i.pl.) of the mouse hind-limb produced a flexor response. The flexor responses were dependent on BK doses (0.02-20 pmol, i.pl.), and were completely abolished by Hoe140, a B2-type BK receptor antagonist. Kyotorphin, an analgesic neuropeptide which shows enkephalin release in brain slices, produced a dose-dependent reduction of the BK-induced nociceptive responses in ranges of 10 pmol to 1 nmol (i.pl.). Such analgesic effects of kyotorphin were reversed by leucine-arginine, a specific kyotorphin receptor antagonist, but not by naloxone. The kyotorphin-analgesia was also abolished by pertussis toxin (PTX) pretreatment. These results suggest that peripheral analgesic effects of kyotorphin are mediated through mechanisms of kyotorphin specific receptor and PTX-sensitive Gi/Go, and that the enkephalin release is not necessary for this analgesia.
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PMID:Peripheral non-opioid analgesic effects of kyotorphin in mice. 940 52

We recently developed a sensitive peripheral analgesic test in mice. Bradykinin, a representative pain-producing substance, when given subcutaneously through a polyethylene tube into the plantar of the limb connected to a transducer, induced a flexor reflex response, in a dose dependent manner. When morphine, a mu-opioid receptor agonist, was added to the plantar through another polyethylene tube, bradykinin-induced responses were completely abolished in a naloxone-reversible manner. These peripheral analgesic effects were also observed with DAMGO, another mu-opioid receptor agonist, and U-69,593, a kappa-opioid receptor agonist, but not DSLET, a delta-opioid receptor agonist. When morphine was given subcutaneously to the back, a potent analgesia in the tail pinch test was observed. Repeated administrations of morphine once per day for 5 days showed a marked tolerance or reduction in morphine analgesia on the 6th day, while there was no significant reduction in the peripheral analgesia of morphine. These findings suggest that tolerance to morphine analgesia is mediated through synaptic plasticity in the central nervous system, but not through a receptor desensitization at the level of the single cell.
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PMID:Lack of tolerance in peripheral opioid analgesia in mice. 958 56