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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During 30 days of thiamine deficiency (TD) feeding, the rat antinociceptive effect (pain threshold) to noxious heat stimulation was significantly increased in proportion to the decrease substance P (SP) fluorescent intensity in the spinal cord. Only a single injection of thiamine HCl (0.5 mg/kg, s.c.) on the early treatment day during TD feeding effectively reversed the analgesic effect to the pair-fed control level. Whereas this reversal effect by thiamine treatment was not found if this treatment was done on the relatively late day. However, either treatment day, except muricide, complete disappearance of various animal behaviours induced by TD was found. These results indicate that, after certain degree of TD development, TD-induced behavioral effects might be reversible, but the afferent nerve fibers might be irreversibly damaged, probably by the similar mechanism as found for an excitotoxin(s) mediated injury in the certain brain region(s). The results also suggest a possibility that SP and an excitotoxin, glutamate, in the dorsal part of the spinal cord greatly contribute to the pain transmission induced by noxious heat stimulation.
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PMID:Immunohistochemical determination of rat spinal cord substance P, and antinociceptive effect during development of thiamine deficiency. 857 71

A prospective study was undertaken to compare the analgesic effect of intra-articular bupivacaine, morphine, or saline in the 24-hour period following cranial cruciate ligament repair in dogs. Thirty-six clinical patients with ruptured cranial cruciate ligaments were randomly assigned to one of three groups. After surgical stabilization, and before skin closure, an intra-articular injection was given; group one (n = 12) received 0.5% bupivacaine HCl at 0.5 mL/kg, group two (n = 12) received morphine at 0.1 mg/kg diluted with saline to a volume of 0.5 mL/kg, and group three (n = 12) received saline at 0.5 mL/kg. Heart rate, respiratory rate, mean arterial blood pressure, cumulative pain score, visual analog pain score, and pain threshold test on both stifles were recorded preoperatively and at 0 to 6 and 24 hours postoperatively. Surgeons and pain scoring investigators were unaware of the intra-articular medication given. Supplemental analgesia, if needed, was provided in the postoperative period according to subjective assessment of patient discomfort. Postoperative pain scores were lowest in the bupivacaine group and highest in the saline group. Pain threshold, measured by applying calibrated loads to the knee, was higher postoperatively in the bupivacaine group than in the saline group. Dogs in the morphine and bupivacaine groups required less supplemental analgesia than dogs in the saline group. The local provision of analgesia reduces the need for systemic drugs with potential side effects. Both intra-articular morphine and intra-articular bupivacaine provided better postoperative analgesia than intra-articular saline, with intra-articular bupivacaine showing the greatest effect.
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PMID:Postoperative analgesia for stifle surgery: a comparison of intra-articular bupivacaine, morphine, or saline. 871 87

Chronic pain remains a problem because it is often misdiagnosed and undertreated. Adverse effects and safety concerns associated with many analgesics have limited the use of these agents and contributed to the undertreatment of pain. With regard to the pharmacologic agents most commonly used to manage pain, centrally acting analgesics (e.g., morphine, codeine) are associated with respiratory depression, tolerance, and dependence, and most nonsteroidal anti-inflammatory drugs (NSAIDs) produce adverse gastrointestinal effects. New to the United States, tramadol HCl, which has been prescribed for almost 2 decades in Europe, is a single-entity, centrally acting analgesic that is effective for the management of moderate to moderately severe pain. Although the mechanism of action of this analgesic is not completely understood, animal models suggest that at least two complementary modes of action appear applicable: (1) binding of parent compound and mono-O-desmethyltramadol (M1 metabolite) to the mu-opioid receptor and (2) weak inhibition of norepinephrine and serotonin reuptake. Clinical experience suggests that tramadol appears to have a low potential for abuse or addiction. Results from clinical trials conducted in the United States as well as European postmarketing surveillance studies indicate that tramadol is an effective analgesic that may have a particularly important role in the management of chronic painful conditions.
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PMID:Pharmacokinetics, efficacy, and safety of analgesia with a focus on tramadol HCl. 876 60

We examined the peripheral adrenergic mechanisms involved in pain induced by alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) plus (+/-)-noradrenaline or prostaglandin E2 and by intraplantar formalin. Agents were injected s.c. into the plantar surface of rats' paws, and the paw lifting and licking response scored. Pain produced by alpha-methyl-5-HT (10 micrograms) plus noradrenaline (10 micrograms) was blocked by pretreatment with the alpha-adrenoceptor antagonists, phentolamine (10 micrograms) and prazocin HCl (alpha 1; 40 micrograms), but not by timolol (beta; 10 micrograms) or idazoxan (alpha 2; 40 micrograms). Phenylepherine, but not clonidine, substituted for noradrenaline to induce pain when combined with alpha-methyl-5-HT. The alpha 1A-adrenoceptor antagonist, WB-4101 (2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane HCl), but not the alpha 1B- adrenoceptor antagonist, chloroethylclonidine, also blocked the pain response produced by alpha-methyl-5-HT plus noradrenaline. Neither of these agents altered pain produced by alpha-methyl-5-HT plus prostaglandin E2 (0.1 microgram). Formalin-induced pain (1%, 50 microliters) was biphasic, and timolol increased the first phase response. The second phase was attenuated by 40% by phentolamine (10 micrograms) injected 10 min before formalin or at the beginning of the second phase; 30 micrograms did not produce a larger effect. Prazosin and WP-4101, but not idazoxan or chloroethylclonidine, also attenuated the second phase. Thus, activation of alpha 1A-adrenoceptors can contribute to pain, but pain induced by alpha-methyl-5-HT plus prostaglandin E2 is independent of adrenergic function, indicating that adrenergic function is not necessary for induction of pain by inflammatory mediators. alpha 1A-Adrenoceptor blockade attenuates pain when administered after development of pain, implying that peripheral adrenergic mechanisms contribute to ongoing maintenance of pain.
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PMID:Contribution of peripheral alpha 1A-adrenoceptors to pain induced by formalin or by alpha-methyl-5-hydroxytryptamine plus noradrenaline. 877 45

The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. It is well established that excitatory amino acids, aspartate and glutamate, are involved in the spinal transmission of nociceptive information and in the development of hyperalgesia. In the present study, intrathecal (i.t.) administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), a structural analog of L-glutamate, produced a dose-dependent behavioural syndrome characterized by caudally directed biting in mice. We demonstrated that peripheral pre-administration of the AMPA receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX, 10-100 mg/kg s.c.) and 1-(4-aminophenyl)-3-methylcarbamoyl-4-methyl-3,4-dihydro-7, 8-methylene-dioxy-5H-2,3-benzo-diazepine-HCl (GYKI 53655, 3-10 mg/kg s.c.), and also of the NMDA receptor antagonist 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine maleate (MK 801, 0.3-1 mg/kg s.c.) reversed this effect. These findings suggest that the hyperalgesia induced by the i.t. injection of AMPA in mice involves the activation of both NMDA and non-NMDA excitatory amino acid receptor sites.
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PMID:Pharmacological characterization of AMPA-induced biting behaviour in mice. 881 40

1. The effect of repeated capsaicin application on the skin of the volar surface of the forearm on the pain sensation and on the increase in blood flow induced by intradermal injection of low pH media or hypertonic solutions was investigated in 13 healthy volunteers. 2. Low pH media (4, and 2.5) were obtained by adding HCl to 0.9% saline. Hypertonic solutions (300 and 600 mM) were obtained by adding NaCl to pH 7.4, 0.9% saline. Capsaicin (1% in 50% ethanol) was painted on the volar skin of one forearm, chosen at random, for 7 days. The contralateral forearm was treated with the capsaicin vehicle. Pain was assessed by a visual analogue scale and skin blood flow by a laser doppler flowmeter. 3. Pain sensation and increase in blood flow (both peak and area under the curve) induced by low pH media were markedly reduced in the capsaicin pretreated side. Capsaicin pretreatment also reduced the increase in blood flow, but did not affect the pain response induced by hypertonic saline solutions. 4. Repeated application of capsaicin to the human skin inhibits both the sensory (pain) and 'efferent' (vasodilatation) responses induced by low pH media, whereas it reduces the vasodilatation, but not the pain caused by hypertonic media. 5. Repeated application of capsaicin to the human skin, a therapy used in various diseases, discriminates between sensory, but not 'efferent' responses induced by different stimuli.
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PMID:The effects of repeated dermal application of capsaicin to the human skin on pain and vasodilatation induced by intradermal injection of acid and hypertonic solutions. 882 86

We carried out the controlled, double-blind clinical study on the effect of antacids containing aluminium on the healing of duodenal ulcer (DU) and the morphology of gastric mucosa in 153 patients with duodenal ulcer disease. The patients were treated for 4 weeks with either dihydroxyaluminium-sodium carbonate (Alugastrin) or aluminium and magnesium hydroxides (Alumag) and for comparison with ranitidine or placebo. The clinical usefulness of antacids were assessed according to the following criteria: ulcer healing ratio, disappearance of ulcer pain, drug tolerance both subjective and objective (biochemical analyses) and drug effect on the gastric mucosa (endoscopy, histology and morphometry). The results were compared with results obtained from ranitidine treated patients. We have shown that both antacids speed up the DU healing similarly to ranitidine (71%, 75% and 79% respectively) and significantly better than placebo (47% of cases). All administered drugs diminished subjective symptoms of patients and were well tolerated. Dihydroxyaluminium-sodium carbonate and aluminium and magnesium hydroxides as well as ranitidine were without any trophic effects on the gastric mucosa. Thus, despite differences in the pharmacological action (antacids are gastroprotective drugs, ranitidine inhibits HCl secretion), antacids are similarly effective to ranitidine in the treatment of DU patients. However, ranitidine is more comfortable for the patients and better accepted in the long-term treatment.
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PMID:[A clinical trial on the effect of aluminum containing antacids on the course of duodenal ulcer healing and morphology of the gastric mucosa]. 883 64

Although postoperative pain following laparoscopic cholecystectomy (LC) is less intense than that after open surgery, postoperative morbidity nonetheless increases with LC. The aim of this study was to investigate whether local anesthetic infiltration of trocar sites during LC decreased postoperative pain and, if so, to find the optimum timing for local anesthesia (LA). Seventy patients undergoing LC were randomized into three groups. In the first (control group, n = 25) 3 ml of 0.9% NaCl was subcutaneously infiltrated around each 5-mm trocar site, 4 ml around each 10-mm site. In the second group (n = 20), the same volume of local anesthetic was administered in the same manner prior to surgery, and in the third group (n = 25) an identical dose of local anesthetic was infiltrated at the end of surgery. A visual analog scale was given to all patients, who were asked to record their pain intensity at 1, 3, 5, 7, and 12 h postoperatively. Pethidine HCl 1 mg/kg i.m. was given to those whose pain intensities were greater than 5. The mean pain intensities were 7.6, 5.9, and 5.1 in the control, preoperative, and postoperative LA groups, respectively. In the preoperative LA group, 50% of patients and in the postoperative LA group 28% of patients required analgesics compared with 76% in the control group. The main pain intensities and analgesic requirements were significantly lower in the postoperative LA group compared with other groups. We conclude that local anesthesia during LC reduces postoperative pain and that infiltration of trocar sites following surgery offers better pain relief than local anesthetic given just before the incision.
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PMID:The effect and timing of local anesthesia in laparoscopic cholecystectomy. 889 Apr 20

Conditions such as hyperalgesia can occur days or months after the noxious insult. Substance P (SP) is released in response to noxious stimuli. Given the long-term effects of the N-terminus of SP on putative nociceptive transmitters, we investigated changes in formalin-induced nociception following an accumulation of SP N-terminal metabolites in mice. Pre-treatment with the N-terminal metabolite of SP, SP(1-7), was without effect when injected intrathecally (i.t.) 5 or 30 min before formalin. However, at 24 h, SP(1-7) increased behaviors during Phase 1, indicating hyperalgesia, and attenuated Phase 2 responses, consistent with antinociception. The nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine methyl ester HCl (L-NAME), blocked both hyperalgesic and antinociceptive effects when co-injected with SP(1-7). Consistent with a NO-mediated pathway, L-arginine (L-arg), the N-terminal amino acid of SP and precursor to NO, mimicked the antinociceptive effect of SP(1-7) on Phase 2. The hyperalgesic effect of SP(1-7) in Phase 1, which was not mimicked by L-arg, was prevented by D-SP(1-7), a SP(1-7) antagonist. Thus, SP(1-7) modulates nociception via two distinct NO-mediated pathways. When injected for 7 days, tolerance developed to the antinociceptive effect of SP(1-7) on Phase 2, but not to the hyperalgesic effect on Phase 1. Intraperitoneally injected SP(1-7) also produced hyperalgesia during Phase 1, to which tolerance developed following seven daily injections. Together, these data support the hypothesis that an accumulation of SP N-terminal metabolites, either peripherally or within the spinal cord area, is sufficient for long-term modulation of multiple types of nociception with hyperalgesic responses being most persistent.
Pain 1996 Oct
PMID:Nitric oxide mediates long-term hyperalgesic and antinociceptive effects of the N-terminus of substance P in the formalin assay in mice. 895 39

Propofol has the disadvantage of pain on injection. A higher partition of propofol in the aqueous phase of the preparation causes a higher incidence of pain on injection while addition of 1% lignocaine to propofol reduces pain. The low concentration of this local anaesthetic and the rapid pain relief observed indicates that mechanisms other than local anaesthesia are involved, that is change in pH. We performed a clinical study to investigate the influence of lignocaine and pH on pain during injection of 1% Diprivan. Ten parts of 1% Diprivan were mixed with one part of saline, 1% lignocaine or hydrochloric acid to achieve the same pH as that after addition of lignocaine. Diprivan 1% mixed with 1% lignocaine and with hydrochloric acid gave mean pain ratings (1-10) of 0.32 (SD 0.75) (n = 25) and 0.88 (1.30) (n = 24), respectively. These ratings were significantly lower than ratings after injection of a saline-Diprivan mixture (2.18 (2.06), n = 22). The pH of the 1% Diprivan formulation decreased after mixing with 1% lignocaine. The concentration of propofol in the aqueous phase was lower when 1% Diprivan was mixed with 1% lignocaine (0.376 g litre-1) or HCl (0.392 g litre-1) compared with 1% Diprivan and saline (0.476 g litre-1) mixed in the same proportion. Thus pH changes may modify propofol-induced pain on injection by a mechanism different from the effect of the local anaesthetic on the vascular endothelium. Our findings may explain why lignocaine mixed with propofol causes less pain than injection of lignocaine followed by propofol.
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PMID:Effect of lignocaine and pH on propofol-induced pain. 917 62


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