An Experimental Pain Method Sensitive to Morphine in Man

Smith, Gene M.; Egbert, Lawrence D.; Markowitz, Robert; Mosteller, Frederick; Beecher, Henry K.; Keats, Arthur S.

doi:10.1097/00132586-196708000-00023

Cited by 55 publications

(80 citation statements)

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“…Ischaemic pain, cold pressor pain and pain to electrical stimulations were decreased by morphine [87,[89][90][91][92]. Pain to hypertonic saline was sensitive to modulation from morphine when a high dose was administered [48,53].…”

Section: Figurementioning

confidence: 97%

“…Despite the fact that experimental pain models only explore a limited and differential part of the cascade of processes involved in clinical pain some models predict how the analgesic will behave in the clinic [124]. An example of this is the model of ischaemic muscle pain.This model is thought to mimic clinical inflammatory musculoskeletal pain and for morphine there is consensus between the findings in the model and the clinical situation [91,92]. Another example, showing the limit of experimental pain, is the capsaicin model, thought to mimic neuropathic pain because the evoked hyperalgesia has features (allodynia) that is seen also in the clinic.…”

Section: The Role Of Experimental Pain In Drug Testingmentioning

confidence: 99%

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Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

Staahl

Olesen

Andresen

et al. 2009

Brit J Clinical Pharma

110

131

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AIMExperimental pain models may help to evaluate the mechanisms of action of analgesics and target the clinical indications for their use. This review addresses how the efficacy of opioids can be assessed in human volunteers using experimental pain models. The drawback with the different study designs is also discussed. METHODA literature search was completed for randomized controlled studies which included human experimental pain models, healthy volunteers and opioids. RESULTSOpioids with a strong affinity for the m-opioid receptor decreased the sensation in a variety of experimental pain modalities, but strong tonic pain was attenuated more than short lasting pain and non-painful sensations. The effects of opioids with weaker affinity for the m-opioid receptor were detected by a more narrow range of pain models, and the assessment methods needed to be more sensitive. CONCLUSIONThe way the pain is induced, assessed and summarized is very important for the sensitivity of the pain models. This review gives an overview of how different opioids perform in experimental pain models. Generally experimental pain models need to be designed with careful consideration of pharmacological mechanisms and pharmacokinetics of analgesics. This knowledge can aid the decisions needed to be taken when designing experimental pain studies for compounds entering phase 1 clinical trials.

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Section: Figurementioning

confidence: 97%

Section: The Role Of Experimental Pain In Drug Testingmentioning

confidence: 99%

Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

Staahl

Olesen

Andresen

et al. 2009

Brit J Clinical Pharma

110

131

View full text Add to dashboard Cite

show abstract

“…Because 5-HT has been impli cated in central pain (see Richardson 1992), and because impairments in 5-HT function have been associated with alterations in nociception (see Messing and Lytle 1977), pain measures were also examined in MDMA users. Nociceptive function was assessed by the sub maximum-effort tourniquet technique for inducing isch emic pain in humans (Smith et al 1966). Three pain measures were obtained: (1) the subject's frrst self-rating of pain was used as a measure of pain "sensitivity; " (2) the time from the start of the test until the subject chose to abort testing was used as a measure of a subject's pain "endurance" (with a maximum score of 20); and (3) the total pain score (the sum of all the values taken at 30-second intervals for the duration of the test) was used as a measure of a subject's pain "tolerance.…”

Section: Outcome Measuresmentioning

confidence: 99%

Serotonin Neurotoxicity after (±)3,4-Methylenedioxymethamphetamine (MDMA; “Ecstasy”): A Controlled Study in Humans

McCann¹,

Ridenour

Shaham

et al. 1994

Neuropsychopharmacol

305

174

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(±)3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy"), an increasingly popular recreational drug, is known to damage brain serotonin 5-hydroxytryptamine (5-HT) neurons in experimental animals. Whether MDMA is neurotoxic in humans has not been established. Thirty MDMA users and 28 controls were admitted to a controlled inpatient setting for measurement of biologic and behavioral indexes of central 5-HT function. Outcome measures obtained after at least 2 weeks of drug abstinence included concentrations of monoamine metabolites in cerebrospinal fluid (CSF), prolactin responses to L-tryptophan, nociceptive responses to ischemic pain, and personality characteristics in which 5-HT has been implicated (i.e., impulsivity and aggression). Subjects with a history of MDMA exposure had lower levels of CSF 5-hydroxyindoleacetic acid (the

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“…This might be due to the fact that most of the methods used for the induction of pain do not produce inflammation or substantial tissue damage and the mechanism, by which nonsteroidal anti-inflammatory agents mainly act, i.e., by inhibiting prostaglandin synthesis, thus might not come into play. It was possible to discriminate the effects of such drugs under double-blind ronditions from those of placebo in only a few s udies: acetylsalicylic acid 600 mg was found to alleviate ischaemic fore-arm pain induced by the submaximum effort tourniquet method (Smith et al, 1966) significantly better than placebo (Smith & Beecher, 1969) and tolmetin 200 mg, as well as a combination of tolmetin 100 mg and paracetamol 400 mg, increased threshold and tolerance to electrically induced cutaneous pain significantly more than did placebo (Stacher et al, 1979a). In a single-blind study on healthy volunteers, the sensation threshold to electrical stimulation of the tooth pulp was found to be significantly higher after administration of each proquazone 600 mg, indomethacin 100 mg, diclofenac 100 mg, naproxen 500 mg, and phenylbutazone 400 mg than after placebo (Gabka, 1979).…”

Section: Introductionmentioning

confidence: 99%

Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 and 150 mg diclofenac sodium in comparison with 60 mg codeine and placebo.

Stacher¹,

Steinringer²,

Schneider³

et al. 1986

Brit J Clinical Pharma

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Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 2 Experimental pain models have been shown to discriminate reliably between the effects of opioid analgesics and placebo but their sensitivity to nonsteroidal antiinflammatory agents is disputed. 3 This study investigated whether it would be possible by using electrically and thermally induced cutaneous pain to discriminate reliably the effects of single oral doses of 75 and 150 mg diclofenac sodium on the one hand and 60 mg codeine on the other from those of placebo. 4 Forty-eight healthy subjects participated each in four experiments in which they received, in random double-blind fashion, each of the treatments. Every experiment comprised eight series of measurements, two before and six after drug administration, carried out at 30 min intervals. 5 Diclofenac sodium produced significant dose-related increases of threshold and tolerance to electrically and threshold to thermally induced pain. 6 Codeine 60 mg was significantly superior to placebo in all pain measures. Its analgesic effects were stronger than those of diclofenac 75 mg but weaker than those of diclofenac 150mg. 7 Neither 150 mg nor 75 mg diclofenac caused more side effects than placebo, whereas codeine 60 mg elicited a high frequency of side effects. No severe adverse effects occurred after any one treatment. 8 The results suggest that both electrically and thermally induced cutaneous pain are well suited to evaluate analgesic effects not only of opioids but also of nonsteroidal antiinflammatory drugs.

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An Experimental Pain Method Sensitive to Morphine in Man

Cited by 55 publications

References 0 publications

Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

Serotonin Neurotoxicity after (±)3,4-Methylenedioxymethamphetamine (MDMA; “Ecstasy”): A Controlled Study in Humans

Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 and 150 mg diclofenac sodium in comparison with 60 mg codeine and placebo.

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