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)

Intradermal injection of the capsaicin analogue, NE-21610 (Procter and Gamble), inactivates nociceptors but not low-threshold mechanoreceptors in monkey. The present study examined the effects of cutaneous NE-21610 on heat and mechanical sensation in normal human volunteers. In the first series of experiments, subjects received intradermal (i.d.) injections (30 microliters) of the vehicle alone or with the drug (0.3, 3.0, 10 micrograms) into different sites on the volar forearm. Subjects were randomly assigned to 1 of 3 protocols to examine drug-evoked pain (n = 8), or alterations in pain to heat (n = 8) or mechanical (n = 8) stimuli induced by the drug. An additional 7 subjects rated pain to mechanical and heat stimuli before and after subcutaneous (s.c.) injections (300 microliters) of the vehicle or drug (100 micrograms). The peak pain occurred at the time of injection, was of short duration, and was similar for vehicle and drug injections. A mild, dose-related pain followed that lasted up to 2 h. Von Frey thresholds for detection, sharpness, and pain at the injection site (measured 24 h after injection) were not significantly altered by either i.d. or s.c. drug administration. However, pain to stepped heat stimuli was reduced in a dose-dependent fashion for both types of injection. At the highest drug doses, analgesia to heat stimuli was still present 1 week after injection. Recovery of heat sensitivity occurred several weeks after injection. This dissociated loss of heat but not mechanical pain sensibility may be due to: (1) a selective action of the drug on heat transducers in nociceptors responsive to both heat and mechanical stimuli, or (2) a selective action on that subset of nociceptors responsible for signaling heat-evoked pain.
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PMID:Cutaneous injection of the capsaicin analogue, NE-21610, produces analgesia to heat but not to mechanical stimuli in man. 764 43

Pre-emptive treatment with an i.v. infusion of morphine 10 mg at induction reduces postoperative analgesic requirement and wound hypersensitivity compared with the same dose administered at the end of operation. Increasing the dose of preemptive morphine may potentially reduce postoperative pain further, while administering morphine at the end of operation, in addition to the beginning, may reduce pain generated by the sensory activity elicited from the wound in the immediate postoperative period. To examine this we have conducted a randomized, double-blind study in patients undergoing abdominal hysterectomy to compare the effect of morphine 20 mg administered before operation with 10 mg at induction and 10 mg on closure of the peritoneum. Postoperative pain was assessed by visual analogue score (VAS) at rest and on movement and by total morphine consumption administered by patient-controlled analgesia (PCA). Wound sensitivity was assessed by von Frey pain thresholds. Both groups had similar morphine consumption, VAS scores and touch and pain thresholds, and in both, secondary hyperalgesia was prevented. Nausea and vomiting scores were higher in the 20-mg group. There was no significant difference between the two groups and neither regimen appeared to offer obvious clinical advantages compared with a lower dose (10 mg) morphine analgesic strategy. Therefore, there may be a ceiling effect to the production of pre-emptive analgesia by morphine.
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PMID:Is there any clinical advantage of increasing the pre-emptive dose of morphine or combining pre-incisional with postoperative morphine administration? 773 57

In a human acid pain model, which uses continuous intradermal pressure infusion of a phosphate-buffered solution (pH 5.2) to induce localized non-adapting pain, the flow was adjusted to result in constant pain ratings of about 20% or 50% on a visual analog scale (VAS). Six volunteers in each group participated in 4 different placebo-controlled double-blind cross-over studies to measure rapidly evolving cutaneous analgesia from topically applied new ointment formulations of acetylsalicylic acid (ASA) and salicylic acid (SA) as well as of commercial ibuprofen and benzocain creams. Similar, log-linear dose-response curves were found for both ASA and SA, significant in effect at 3 g/kg and higher drug contents and reaching saturation level at 15 or 30 g/kg, respectively, which, 20 min after application, caused a mean pain suppression of 95% using ASA and 80% using SA. Half-maximal effects were achieved using 3 g/kg ASA or 15 g/kg SA. The SA action was also clearly slower to develop. With an increased flow of the acidic buffer, producing lower effective tissue pH and more intense pain, the effect of ASA and SA decreased to 73% pain suppression. A competitive mechanism of both drug effects was suggested by the fact that, with 15 g/kg ASA and SA, pain reduction could be reversed by increasing the buffer flow by a factor of 1.75, on average. Commercial ibuprofen (50 g/kg) and benzocain creams (100 g/kg) were comparably as effective as ASA and SA, but the local anesthetic caused a loss of all cutaneous sensations while the touch threshold (von Frey) under the specific analgesics was the same as under the placebo ointment. Thus, topical applications of non-steroidal anti-inflammatory drugs (NSAIDS) dissolved in different ointment formulations have proven dose-dependently effective and specific in suppressing experimental acidotic pain by a local and competitive mechanism.
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PMID:Dose-dependent competitive block by topical acetylsalicylic and salicylic acid of low pH-induced cutaneous pain. 886 48

Patients with unilateral (n = 14) and bilateral (n = 4) herniorrhaphy participated in this study. With bilateral herniorrhaphy, at the end of the surgery, the wound was infiltrated with a solution of bupivacaine 0.5% and ketamine 0.3% on one side and a solution of bupivacaine 0.5% only, on the other. With unilateral herniorrhaphy, the patients were randomly assigned to one of two groups (n = 7). One group at the end of the surgery received the infiltration with a solution of bupivacaine 0.5% and ketamine 0.3%, the other group received the infiltration with a solution of bupivacaine 0.5% only. The duration of the local anesthetic (response to a von Frey filament) and postoperative analgesic (time to mild spontaneous pain) effects of the infiltrations, as well as wound pain threshold 24 h after surgery (pressure algometry), were determined. In patient with unilateral herniorrhaphy, the addition of ketamine for wound infiltration enhanced the duration of infiltration anesthesia (206 +/- 76 versus 343 +/- 108 min, P < 0.02) and analgesia (240 +/- 45 versus 420 +/- 151 min, P < 0.03). Similar enhancement of the local anesthetic effect was observed in patients with bilateral herniorrhaphy. The increase in pain threshold to pressure on the wound with the addition of ketamine was evident in bilateral herniorrhaphy patients and also with a combination of bilateral and unilateral results (1.39 +/- 0.40 versus 2.35 +/- 0.92 kg, P < 0.02). In the group of five volunteers, the subcutaneous infiltration with 0.3% ketamine produced a local anesthetic effect lasting only 10-20 min. The results indicate that ketamine acting via a peripheral mechanism can profoundly enhance anesthetic and analgesic actions of a local anesthetic administered for infiltration anesthesia.
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PMID:Ketamine enhances local anesthetic and analgesic effects of bupivacaine by peripheral mechanism: a study in postoperative patients. 1256 Mar 18

Previously we demonstrated the use of chemical (topical acetic acid), thermal (radiant heat) and mechanical (von Frey filament) stimuli as quantifiable behavioral response assays in the northern grass frog, Rana pipiens. Furthermore, response thresholds in all of these sensory modalities are significantly elevated by systemic morphine injections, which can be antagonized by naltrexone. The present study employed these three sensory assays to assess changes in chemical, mechanical and thermal sensitivities following spinal administration of mu, delta and kappa opioids. Significant elevations were observed across all three sensory modalities in each subtype category and these effects were abolished by prior systemic administration of naltrexone. However, naltrexone antagonism of morphine produced hyperalgesia in both the mechanical and thermal modalities. The results support other recent work demonstrating that the spinal site for opioid analgesia is present in amphibians and that the thermal, mechanical and acetic acid assays are measures of true nociceptive activity in the amphibian.
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PMID:Spinal mu, delta and kappa opioids alter chemical, mechanical and thermal sensitivities in amphibians. 939 36

We studied 60 patients undergoing operation on the kidney with combined general and epidural anaesthesia, in a double-blind, randomized, controlled study. Patients were allocated to receive a preoperative bolus dose of ketamine 10 mg i.v., followed by an i.v. infusion of ketamine 10 mg h-1 for 48 h after operation, or placebo. During the first 24 h after surgery, all patients received 4 ml h-1 of epidural bupivacaine 2.5 mg ml-1. From 24 to 48 h after operation, patients received epidural morphine 0.2 mg h-1 preceded by a bolus dose of 2 mg. In addition, patient-controlled analgesia (PCA) with i.v. morphine (2.5 mg, lockout time 15 min) was offered from 0 to 48 h after operation. Patients who received ketamine felt significantly more sedated at 0-24 h, but not at 24-48 h after operation, compared with patients who received placebo (P = 0.002 and P = 0.127, respectively). There were no significant differences in pain (VAS) at rest, during mobilization or cough, PCA morphine consumption, sensory block to pinprick, pressure pain detection threshold assessed with an algometer, touch and pain detection thresholds assessed with von Frey hairs, peak flow or side effects other than sedation. The power of detecting a reduction in VAS scores of 20 mm in our study was 80% at the 5% significance level. We conclude that we were unable to demonstrate an (additive) analgesic or opioid sparing effect of ketamine 10 mg h-1 i.v. combined with epidural bupivacaine at 0-24 h, or epidural morphine at 24-48 h after renal surgery.
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PMID:Effect of i.v. ketamine in combination with epidural bupivacaine or epidural morphine on postoperative pain and wound tenderness after renal surgery. 1019 80

Dextromethorphan is an N-methyl-D-aspartate (NMDA) receptor antagonist which has been shown to inhibit the development of cutaneous secondary hyperalgesia after tissue trauma. We studied 60 ASA I-II patients undergoing total abdominal hysterectomy in a randomized, double-blind, placebo-controlled study. Patients received either dextromethorphan 27 mg capsules, two doses before operation and three doses in the first 24 h after operation, or placebo. Visual analogue pain scores (VAS) at 24 and 48 h were assessed at rest, on coughing and on sitting up, and were not significantly different between groups. Morphine consumption from a patient-controlled analgesia (PCA) device was also not significantly different between groups. Evidence of secondary hyperalgesia was assessed with von Frey hairs 10 cm above the Pfannenstiel incision. Both groups of patients exhibited evidence of secondary hyperalgesia after 24 and 48 h but there were no significant differences between groups. There was also no difference between groups in VAS scores at 1 month.
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PMID:Dextromethorphan and pain after total abdominal hysterectomy. 1019 85

The aim of this study was to investigate the analgesic effects of epidural opioids in neonatal rat pups. The contribution of individual opioid receptor subtypes in the spinal cord to analgesia at different developmental stages was investigated using epidural mu (morphine sulphate), delta (DPDPE) and kappa (U69593) opioid receptor agonists in neonatal rats aged postnatal day (P) 3, 10 and 21. Thresholds for flexion withdrawal reflexes to mechanical stimuli (von Frey hairs) and to noxious heating of the hind paw were low in neonates and increased with postnatal age. The analgesic action of each opioid receptor agonist followed an individual developmental pattern. In mechanical tests, all three opioid agonists were considerably more efficacious analgesics in younger animals and ED50s at P3 were always lower than at P21. In heat tests, the pattern differed. The efficacy of the kappa opioid agonist decreased with postnatal age, morphine efficacy increased over the same period and the effects of the delta agonist remained relatively unchanged. The distribution and concentration of tritiated morphine in the spinal cord following epidural administration did not alter significantly with postnatal age, suggesting that opioid access is not a major determinant of the effects reported here. It is concluded that whereas heat pain is particularly sensitive to spinal kappa opioids in neonates, mechanical sensory thresholds are generally sensitive to all spinal opioids in the newborn. The differing epidural opioid requirements compared to older subjects is likely to be due to developmental changes in spinal cord opioid receptor distribution or pharmacology.
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PMID:Epidural opioid analgesia in infant rats I: mechanical and heat responses. 1042 56

The aim of this study was to investigate the analgesic effects of epidural opioids upon persistent pain sensitivity in neonatal rat pups. Two models of persistent pain were used, subcutaneous injection of carrageenan, and topical application of capsaicin cream, both to the hind paw. The contribution of individual opioid receptor subtypes in the spinal cord to analgesia were tested at different developmental stages using epidural mu (morphine sulphate), delta (DPDPE) and kappa (U69593) opioid receptor agonists in neonatal rats aged P (postnatal day) 3, 10 and 21. Rat pups at all three ages displayed a reduction in mechanical (von Frey hair) threshold following carrageenan-induced inflammation of the hind paw that was evident at 3 h and was still present 5 h after application. This effect was greatest in magnitude at P21. This response was blocked by low doses of all three agonists at all ages, relative effectiveness varying with age. Comparison with potencies in acute tests (Marsh, D., Dickenson, A., Hatch, D. and Fitzgerald, M., Epidural opioid analgesia in infant rats I: mechanical and heat responses, Pain 82 (1999) 23-32) show that opioid potency is significantly greater in the presence of carrageenan inflammation at all ages. Topical capsaicin application to the hind paw produced a significant fall in withdrawal latencies to noxious heat. Generally, epidural opioid agonists did not block this C-fibre induced sensitization except at P3, when morphine and DPDPE did prevent the fall in threshold in a dose dependent manner. The results show that newborn rat pups are capable of displaying both allodynia and hyperalgesia following experimental inflammation that is blocked by epidural mu, delta and kappa opioids. The opioid potency is enhanced compared with antinociception in acute tests. This is not observed following capsaicin hyperalgesia and is therefore not a general consequence of C fibre induced increases in central excitability but relies upon mechanisms special to inflammatory pain.
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PMID:Epidural opioid analgesia in infant rats II: responses to carrageenan and capsaicin. 1042 57

Cannabinoid receptor (CB1) agonists strongly inhibit behavioral responses to acute noxious stimuli, but their effects on behavioral responses in persistent pain states are less clear. Here, we examined the effects of intrathecal (i.t.) administration of a CB1 agonist, WIN55,212-2, on mechanical allodynia (decreased withdrawal threshold) produced by injections of complete Freund's adjuvant (CFA) in the plantar surface of the rat hindpaw. We measured mechanical thresholds with calibrated von Frey filaments before and after CFA and used Fos expression as a marker of the activity of spinal cord neurons during inflammation and in response to a CB1 antagonist. One day post CFA-induced injury, mechanical sensitivity was significantly increased in the hindpaw ipsilateral to the CFA injection, as was the number of neurons that express Fos. Intrathecal injection of WIN55,212-2, significantly, reversed the allodynia at doses that had no effect on the mechanical threshold of the contralateral paw of CFA-treated or the withdrawal thresholds in naive animals. This effect was blocked by coadministration of the CB1 antagonist, SR141716A, with WIN55212-2. By itself, SR141716A, had no effect on mechanical thresholds in normal animals. In inflamed animals, SR141716A did not further reduce mechanical thresholds in the inflamed paw, but it significantly enhanced mechanical sensitivity 'contralateral' to the inflammation. Furthermore, i.t. injection of SR141716A increased Fos expression in both normal and inflamed animals, to a different extent in different laminae. In normal animals, the increase was primarily in laminae V-VI and in the ventral horn; in animals with persistent inflammation SR141716A increased the number of Fos neurons in laminae I-II and V-VI. These results demonstrate that WIN55212-2 reverses inflammation-induced allodynia at doses that do not produce analgesia and that SR141716A differentially affects the pattern of Fos expression in the spinal cord, depending on the presence or absence of inflammation. Taken together, these results suggest that the CB1 receptor system is tonically active in the spinal cord under normal conditions and that its activity is increased in response to injury.
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PMID:Spinal cannabinoids are anti-allodynic in rats with persistent inflammation. 1046 24


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