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)

To study the hypothesis that endogenous adenosine is a mediator of the ischaemic pain sensation, the effect of the adenosine receptor blocker theophylline (5.5 mg of the ethylendiamine salt.kg-1 intravenously) was tested in a placebo controlled double blind cross over study (placebo/theophylline/placebo or placebo/placebo/theophylline) in five healthy volunteers. Ischaemic work was performed with a spring loaded hand ergometer (1 Hz). The pain sensation was continuously reported using the Borg scale. Blood flow was measured by occlusion plethysmography. Pain was reported 18 (SEM 2.4) s after starting the ischaemic work and increased continuously to a maximum after 129(18) s (placebo). Theophylline at a plasma concentration of 75(7) mumol.litre-1 decreased the pain sensation in relation to working time. With theophylline, 12(3)% more work (p less than 0.01) was performed for the same reported pain estimate. Blood flow increased from a basal level of 52(9) to 495(55) ml.min-1.100 ml-1 30 s after work and returned to normal within 30-40 min. Theophylline did not affect blood flow. In conclusion, theophylline has a small but significant inhibitory effect on the ischaemic pain sensation compatible with a hyperalgesic effect of adenosine.
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PMID:Theophylline decreases pain in the ischaemic forearm test. 269 16

The tricyclic anticonvulsant carbamazepine (CBZ) is effective in pain and affective disorder, but the mechanism of action for this drug has not been defined. Recently it was reported that CBZ had interaction with adenosine receptor, which is related to the inhibition of release of neurotransmitter. In the present study, we investigated the in vitro effects of CBZ and other drugs upon adenosine receptor binding using 3H-L-phenylisopropyladenosine (A1) and 3H-N-ethylcarboxamidoadenosine (A2). The following results were obtained: CBZ and its derivative oxcarbazepine inhibit 3H-PIA binding at therapeutic plasma level (20-30 microM) more than they inhibit 3H-NECA binding; Theophylline and caffeine, methylxanthines, which are adenosine antagonists, inhibit both bindings; Other anticonvulsants such as phenobarbital, phenytoin and valproate and still other psychotropic drugs such as diazepam, imipramine and chlorpromazine have little or no effect on both bindings. These findings suggest that anticonvulsive and sedative effects of CBZ and its derivatives appear due to action on adenosine receptors (A1 and partially A2) at the therapeutic level and methylxanthines have stimulant and convulsant effects due to occupation on both A1 and A2 adenosine receptors.
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PMID:Interaction of carbamazepine and other drugs with adenosine (A1 and A2) receptors. 309 20

Morphine is the most potent opioid analgesic currently available and its use is increasing for treatment of severe pain, however, long-term morphine exposure induces physical dependence/tolerance. Although the mechanisms underlying this phenomenon have not been established, several biochemical changes including intracellular cAMP systems and Ca2+ mobilization have been suggested. To evaluate the contribution of cAMP, we investigated the effects of nefiracetam [N-(2,6-dimethyl-phenyl)-2(2-oxo-1-pyrrolidinyl)acetamide] and phosphodiesterase inhibitors (theophylline, enprofylline and rolipram) on the development of morphine dependence/tolerance. Mice administered morphine (6 or 10 mg/kg, s.c.) twice daily for 5 days, showed withdrawal signs (jumping, diarrhea and body weight loss) after naloxone challenge (5 mg/kg, i.p.), indicating the physical dependence to morphine. Further, the tolerance to antinociceptive effect of morphine was observed in these mice on the tail-flick test. However, coadministration of nefiracetam (5 or 10 mg/kg, p.o.), enprofylline (30 mg/kg, p.o.) and rolipram (0.3 or 1 mg/kg, i.p.) with morphine during the pretreatment period, significantly reduced the withdrawal signs, moreover, the tolerance was significantly attenuated. Acute administration of nefiracetam failed to reduce the withdrawal signs and did not affect the antinociceptive effect of morphine in morphine-naive mice. Theophylline (3 or 10 mg/kg, p.o.) tended to attenuate the development of morphine dependence/tolerance. The present findings suggest that coadministration of compounds which increase cAMP level with morphine may be a useful strategy to attenuate the development of morphine dependence/tolerance in the clinic.
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PMID:A therapeutic strategy to prevent morphine dependence and tolerance by coadministration of cAMP-related reagents with morphine. 981 8

The effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on pain sensitivity, on morphine analgesia, on morphine tolerance and withdrawal were investigated in mice. The heat-radiant tail-flick test was used to assess antinociceptive threshold. Intracerebroventricular (i.c.v.) administration of PACAP alone had no effect on pain sensitivity but in a dose of 500 ng, it significantly diminished the analgesic effect of a single dose of morphine (2.25 mg/kg, s.c.). PACAP (500 ng, i.c.v.) significantly increased the chronic tolerance to morphine and enhanced the naloxone (1 mg/kg, s.c.)-precipitated withdrawal jumping. Theophylline (1 mg/kg, i.p.) pretreatment significantly enhanced the effect of PACAP on morphine analgesia but the effects of PACAP on tolerance and withdrawal were unaffected upon theophylline administration. On the grounds of our previous studies with vasoactive intestinal polypeptide (VIP), it appears that different receptors are involved in the effects of PACAP in acute and chronic morphine actions. Our results indicate that PACAP-induced actions likely participate in acute and chronic effects of morphine and suggest a potential role of PACAP in opioid analgesia, tolerance and withdrawal.
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PMID:The effects of pituitary adenylate cyclase-activating polypeptide on acute and chronic morphine actions in mice. 1240 15

Visceral hypersensitivity may play a role in the pathogenesis of functional chest pain, although the underlying mechanism(s) is unknown. We investigated the effects of theophylline, an adenosine receptor antagonist, on sensory perception and biomechanical properties of esophagus in patients with functional chest pain. Esophageal balloon distention was performed using impedance planimetry in 21 consecutive patients with functional chest pain. Patients found to have a hypersensitive esophagus received intravenous theophylline and balloon distension was repeated. If the hypersensitivity improved, oral theophylline was prescribed for three months as an open label trial. Balloon distension reproduced typical chest pain in 16 (76%) patients at thresholds suggestive of hypersensitivity. After theophylline infusion, pain thresholds increased in 12 (75%) patients. Median threshold pressures for discomfort and pain improved (P < 0.01). Cross-sectional area increased (P < 0.05) and the tension/strain association shifted to the right (P < 0.01). Seven of eight patients reported sustained improvement in pain after oral theophylline. Theophylline may ameliorate chest pain in patients with hypersensitive esophagus, possibly by altering adenosine-mediated nociception.
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PMID:An open-label trial of theophylline for functional chest pain. 1249 99