Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrogen peroxide is an effective and commonly used contact lens disinfectant that is also used as a preservative in certain ocular medications. We describe the effects of hydrogen peroxide on the cornea and anterior chamber following its topical application via a contact lens or as drops. The conditions for interaction of hydrogen peroxide with corneal and palpebral tissues and its accumulation within the aqueous humor are detailed. Values are given for thresholds at which hydrogen peroxide in specified concentrations, volumes, locations, and durations of exposure can cause ocular pain, swelling of the corneal stroma, damage to the endothelium, and penetration of the compound to the anterior chamber. The cornea and the palpebral tissues, together with the tear film, form a highly effective barrier and detoxifying system that, except under extreme, accidental circumstances, prevents both extra- and intraocular damage from use of hydrogen peroxide in contact lens care or in medications.
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PMID:Topical hydrogen peroxide and the safety of ocular tissues. 837 42

1. Kallidin (5-500 nmol), hypertonic saline (0.9-20% NaCl) or low pH medium (citric acid: pH 2.5-1) applied (50 microliters) to the human nasal mucosa produced a pain response (evaluated by a visual analogue scale) that was related to the concentration of the peptide, NaCl or hydrogen ions, respectively. 2. Application (50 microliters) of capsaicin (50 nmol) to the human nasal mucosa produced overt pain. After repeated administrations (once a day for 5-7 days) to one nostril this effect underwent almost complete desensitization, while in the contralateral nostril, treated with the vehicle, the response to capsaicin was unaffected. 3. The pain response produced in the human nasal mucosa by topical application (50 microliters) or kallidin (50-500 nmol), NaCl (10-20%) or citric acid (pH 1.5-1) solutions was then studied before and after local capsaicin desensitization. 4. The pain response to pH 1.5 or 1 citric acid was markedly reduced (by 60% and 75%, respectively) in the capsaicin-treated nostril. However, the pain response to 10% or 20% NaCl or the mild pain response to 50 or 500 nmol kallidin were unaffected by capsaicin pre-treatment. 5. The present results suggest that prolonged topical capsaicin treatment to the human nasal mucosa may lead to selective desensitization to certain algesic stimuli such as capsaicin itself and hydrogen ions.
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PMID:Capsaicin-desensitization to the human nasal mucosa selectively reduces pain evoked by citric acid. 844 36

The ability of a competitive (LY274614; (+-)-6-phosphonomethyl-decahydroisoquinolin-3-carboxylic acid) and a noncompetitive (MK801; [(+)-5 methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate) N-methyl-D-aspartate receptor antagonist to modulate the development of tolerance to morphine's antinociceptive (analgesic) effects was assessed by using hot-plate latency in rats. Concurrent treatment with LY274614 or MK801 by continuous s.c. infusion significantly attenuated the development of morphine tolerance produced by twice daily injections of morphine (10 mg/kg s.c.). This attenuation of morphine tolerance by LY274614 was dose-dependent, 12 or 24 mg/kg/24 hr s.c. infusion). Additionally, animals tested 1 week after the discontinuation of all drug treatments were observed to retain their analgesic sensitivity to morphine, whereas control animals remained relatively tolerant. These results suggest that LY274614 and MK801 do not alter the expression of tolerance but actually modify the development of morphine tolerance. Morphine-tolerant animals infused with LY274614 for 7 days regained their analgesic sensitivity to morphine. Furthermore, LY274614 also reversed the development of tolerance and restored morphine sensitivity in tolerant animals that continued to receive morphine. The demonstration that LY274614 can prevent and reverse the development of morphine tolerance without reducing the analgesic response suggests that the adaptive system involved in the development and maintenance of tolerance requires a functional N-methyl-D-aspartate receptor. LY274614 lacks the phencyclidine-like side effects seen with MK801, and this may favor the clinical development of this competitive N-methyl-D-aspartate receptor antagonist as an adjunct for patients receiving chronic opioids for pain management.
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PMID:Attenuation and reversal of morphine tolerance by the competitive N-methyl-D-aspartate receptor antagonist, LY274614. 845 Apr 53

Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier and the potential to antagonize the peripherally mediated effects of opioids. The effectiveness of methylnaltrexone in preventing morphine-induced changes in gastrointestinal motility and transit without affecting analgesia was evaluated in humans. Twelve healthy volunteers were given intravenous placebo, placebo plus 0.05 mg/kg morphine, or 0.45 mg/kg methylnaltrexone plus 0.05 mg/kg morphine. Oral-cecal transit time was assessed by the pulmonary hydrogen measurement technique, and analgesia was measured with use of the cold-pressor test. Morphine significantly increased oral-cecal transit time from 104.6 +/- 31.1 minutes (mean +/- SD) to 163.3 +/- 39.8 minutes (p < 0.01). Methylnaltrexone prevented 97% of morphine-induced increase in oral-cecal transit time (106.3 +/- 39.8 minutes; not significant compared with baseline; p < 0.01 compared with morphine alone). Methylnaltrexone did not affect the analgesic effect of morphine on both pain intensity and pain bothersomeness ratings. At a higher dose of morphine (0.1 mg/kg), our preliminary results indicated that 0.45 mg/kg methylnaltrexone also prevented the morphine-induced delay in oral-cecal transit time, with no effect on analgesia. Methylnaltrexone may be a useful adjunct to opioids for the relief of opioid-induced constipation.
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PMID:Methylnaltrexone prevents morphine-induced delay in oral-cecal transit time without affecting analgesia: a double-blind randomized placebo-controlled trial. 861 93

To study the role of protons in ischemic muscle pain we employed the "submaximal effort tourniquet technique' and, in a second attempt, an intramuscular pressure infusion of acid phosphate buffer. The pH measured in the forearm skin covering the muscles at work during the tourniquet test continuously dropped to a mean value of pH 7.00 +/- 0.26, starting 1 min after the contractions, while the pain increased in direct correlation with the hydrogen ion concentration (r = 0.96). After restoring the blood supply, the intradermal proton concentration decreased more slowly than the muscular pain. The same subjective quality of deep muscular pain was achieved with pressure infusion of acid phosphate buffer (pH 5.2) into the forearm muscles. Constant flow rates evoked constant, apparently non-adapting magnitudes of pain with a log-linear stimulus-response relationship (r = 0.93). Changes in flow rate were followed by changes in pain ratings with a certain phase lag. We conclude that muscular pain induced by infusion of acidic phosphate buffer and pain from ischemic contractions are generated through the same mechanisms based on the algogenic action of protons.
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PMID:Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia? 873 2

A dose-ranging study of the use of oral naloxone in opioid-related constipation in patients with far-advanced cancer is reported. Naloxone doses were calculated as a percentage of the morphine dose each patient was receiving. Seventeen patients entered the first phase of the study, which had a randomised, double-blind design. Outcome measures were small bowel transit time (SBTT) measured by the lactulose/hydrogen breath test, pain scores and the occurrence of adverse events. One subject was excluded before receiving naloxone. No significant difference between placebo and naloxone occurred in the 14 remaining patients receiving total daily doses of naloxone 10% or less of the 24 h dose of morphine. Two further patients experienced a marked laxative effect with naloxone at 20% of the 24 h dose of morphine. In one of these, SBTT was available and was unchanged from placebo. The other declined to continue with SBTT measurement. Phase two of the study had an open design, in which laxative effects were determined clinically. Naloxone at a maximum dose level of 20% was given to seven patients, up to 40% to two patients and up to 80% to one patient. Four out of the seven patients in the 20% dose level group, and all of the remainder, experienced laxative effects. Two patients experienced symptoms of opioid withdrawal, one of whom also had return of pain. It is concluded that oral naloxone at a daily dose of 20% or more of the prevailing 24 h morphine dose is a potentially valuable therapy for opioid-related constipation. However, opioid withdrawal was observed and it is suggested that initial individual naloxone doses should not exceed 5 mg. Further research is needed into the oral absorption of naloxone, as well as further studies of clinical efficacy and dosing.
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PMID:An investigation of the ability of oral naloxone to correct opioid-related constipation in patients with advanced cancer. 880 Aug 21

The oxygen metabolism of polymorphonuclear leukocytes (PMN) is of importance in local tissue repair processes. Amide local anaesthetics are commonly used to relieve surgical wound pain. The cellular effects of local anaesthetics in vivo is poorly described in the literature. However, interactions between amide local anaesthetics and the oxygen metabolism of leukocytes have been reported. To extend that knowledge, this paper investigates the influence of lidocaine treatment on the production of hydrogen peroxide (H2O2) by leukocyte oxygen metabolism. A soft tissue chamber model in the mouse was used, allowing measurements of the H2O2 production spontaneously and after phorbol myristate acetate (PMA) addition, from two different leukocyte pools. Exudate leukocytes were generally more reactive to PMA stimulation in comparison to tissue chamber adherent leukocytes. Topically administered lidocaine significantly influenced the number of leukocytes in the wound exudate at 24 h postoperatively. Exudate leukocytes, topically exposed to lidocaine, showed an enhanced H2O2 production in comparison to leukocytes receiving lidocaine systemically. At 6 days, the viability and the H2O2 production differed significantly between the group receiving topically applied lidocaine in comparison to placebo. We conclude that the wound healing process may be effected by topically applied lidocaine, administered in clinical doses, at least via interference with leukocyte oxygen metabolism.
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PMID:Leukocyte hydrogen peroxide production in a surgical wound in mice. The effects of an amide local anaesthetic. 889 19

When aircraft cabin occupants are exposed to fire effluent, the first hazard encountered is usually smoke, containing particulates and toxic gases, which cause immediate visual obscuration and painful irritation of the eyes and respiratory tract. This may be followed by incapacitation due to pain or asphyxia, if exposure continues. In smouldering or small, confined, in-flight fires, where the yields of organic irritants and acid gases are likely to be high and exposure times long, then the distressing effects of irritants, lung inflammation, and asphyxia induced by carbon monoxide (CO) are likely to be the main hazards. For post-crash fires, which tend to develop rapidly to flashover, the time available for escape is often limited to a few minutes before conditions become lethal due to the effects of toxic smoke and heat, so that survival depends upon a rapid egress. Visual obscuration and smoke irritancy are important during the early stages in that they may reduce the speed and efficiency of escape. People have been shown to be reluctant to enter smoke-logged areas if these are between them and an exit, and movement speeds are greatly reduced at optical densities above OD/m 0.5, and even more when the smoke is irritant. Once cabin lining and seating materials become heavily involved in the area opposite a cabin breach, then the concentrations of toxic gases, especially CO and hydrogen cyanide, can increase rapidly further down the cabin causing rapid incapacitation of any remaining cabin occupants. This is followed or accompanied by extreme heat, so that deaths result from asphyxia and/or heat shock. For in-flight fires, it is recommended that consideration should be given to reducing the hazard from irritants. For post-crash fires, measures aimed at delaying the involvement of cabin contents (such as spray mist systems) should be considered.
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PMID:Behavioural impairment in smoke environments. 901 39

The brainstem preparation with the trigeminal mandibular nerve attached was isolated from rats postnatal day 0-6 (P0-P6) to test if the potentiation could be induced in neonatal neurons in the trigeminal subnucleus caudalis by stimulation of the primary afferents. The stimulation-induced potentials in 92 neurons recorded extracellularly, and the synaptic potentials in 16 neurons recorded by the whole-cell patch clamp technique were examined. The extracellularly recorded neurons responded to stimulation (0.5 Hz) with either an increase, a decrease, or little change in spike numbers, and were classified as Type 1, Type 2, and Type 3, respectively. Type 1 neurons at P4 and older responded in a low Mg2+ solution with a progressive increase in spike number lasting for several minutes after the cessation of stimulation, i.e., short-term potentiation, STP. This potentiation was antagonized by 20 microM of (+)-MK-801 hydrogen maleate (MK-801) or 25 microM of 2-amino-5-phosphonovaleric acid. In contrast, Type 1 at P3 and younger did not exhibit STP. The age-related distinct response properties were observed between Type 1 neurons at P4-P6 and at P0-P3. The percentage of Type 1 in studied neurons increased from 24% at P0-P3 to 53% at P4-P6. In the intracellular experiment, the mean latency of excitatory postsynaptic potential (EPSP) of recorded neurons indicated that the conduction velocity of the convergent afferents was 0.37 m/s, in the range of C-fiber. Neurons were classified as Type E and Type I. Type E responded with EPSP only, or with both EPSP and inhibitory postsynaptic potentials (IPSP), while Type I responded with IPSP only. In Type E at P4 and older, a single stimulation produced a burst of spike discharges that lasted for several seconds. Stimulation at a hyperpolarized membrane potential showed that aggregated slow EPSPs lay under a burst of spike discharges, and that slow EPSPs, but not a short-latency EPSP, were completely blocked by MK-801. In contrast, Type E at P3 and younger did not evoke a burst of spikes. Morphological examination of recorded neurons showed that the formation of networks was sparse at P1 and rapidly developed up to P4. The results suggest that: (1) short-term potentiation is induced with the development of synaptic network formation in the caudal nucleus at P4 and older; (2) the summation of N-methyl-d-aspartate (NMDA)-mediated slow EPSPs build up a prolonged depolarization; and (3) the brainstem preparation is applicable for neurophysiological studies on the trigeminal pain system.
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PMID:Stimulation-induced responses of the trigeminal caudal neurons in the brainstem preparation isolated from newborn rats. 952 48

Responses of wide dynamic range neurons in the spinal dorsal horn to input from C fibers with various conduction velocities were analyzed. The wide dynamic range neurons studied were located in the laminae IV-VI of the spinal dorsal horn. The C fiber response to stimulation of the superficial peroneal nerve consisted of three components: early, middle, and late. The separation into three components was found to be caused by asynchronous volleys in three different classes of C fibers in the superficial peroneal nerve. The phenomenon of windup was observed to occur always in the late component, frequently in the middle component, and to a far lesser extent in the early component. The early component was augmented by sciatic nerve compression, indicating that the initial part of the C fiber response is suppressed within the spinal cord by an inhibitory effect of A fiber afferent volleys. An intravenous administration of a specific N-methyl-D-aspartate receptor antagonist, MK-801 hydrogen maleate, significantly suppressed the middle and late components of the C fiber response, although the effect on the early component was insignificant. Thus, one can infer that the hyperexcitability of wide dynamic range neurons to input from early components of cutaneous C fiber stimuli will yield hyperpathic symptoms such as paresthesia, hyperalgesia, and allodynia associated with damaged peripheral nerves, and that learning how to inhibit the hyperexcitability of wide dynamic range neurons to input from early components of C fiber stimuli will lead to the curative treatment for neuropathic pain.
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PMID:C fiber responses of wide dynamic range neurons in the spinal dorsal horn. 958 91


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