Transcutaneous iontophoresis of methadone provokes local flushing and thermal hyperalgesia

Drummond, Peter D.; Silva-Rossdeutscher, Evelyn de

doi:10.1007/s00011-003-1188-2

Cited by 7 publications

(4 citation statements)

References 30 publications

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“…Heat pain threshold (HPT) was assessed using a TSAII NeuroSensory Analyzer (Medoc Ltd, Ramat Yishai, Israel) as previously described 17, 42 with a 16×16 mm stimulator. Use of a 16×16mm stimulator was based on our preliminary work showing more consistent development of temporal summation with this smaller probe size compared to the larger (30×30mm) probe (unpublished).…”

Section: Methodsmentioning

confidence: 99%

A New Transient Sham TENS Device Allows for Investigator Blinding While Delivering a True Placebo Treatment

Rakel

Cooper

Adams

et al. 2010

The Journal of Pain

118

133

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This study compared a new transient sham TENS that delivers current for 45 seconds to an inactive sham and active TENS to determine the degree of blinding and influence on pain reduction. Pressure pain thresholds (PPT), heat pain thresholds (HPT), and pain intensities to tonic heat and pressure were measured in 69 healthy adults before and after randomization. Allocation investigators and subjects were asked to identify the treatment administered. The transient sham blinded investigators 100% of the time and 40% of subjects compared to the inactive sham that blinded investigators 0% of the time and 21% of subjects. Investigators and subjects were only blinded 7% and 13% of the time, respectively, with active TENS. Neither placebo treatment resulted in significant changes in PPT, HPT, or pain intensities. Subjects using higher active TENS amplitudes (≥17mAs) had significantly higher PPTs and lower pain intensities to tonic pressure than subjects using lower amplitudes (<17mAs). HPTs and pain intensities to tonic heat were not significantly changed. The transient TENS completely blinds investigators to treatment and does not reduce pain, thereby providing a true placebo treatment.

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Section: Methodsmentioning

confidence: 99%

A New Transient Sham TENS Device Allows for Investigator Blinding While Delivering a True Placebo Treatment

Rakel

Cooper

Adams

et al. 2010

The Journal of Pain

118

133

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“…Previous studies demonstrated the role of the skin opioid receptors in peripheral analgesia induced by various opioids in rhesus monkeys [9–11], but also most recently in humans after transcutaneous iontophoresis of methadone [12] or intradermal injections of fentanyl [13]. It is difficult to make a direct comparison between our negative results and the positive analgesic results obtained by other authors because of the considerable differences not only in the opioid administration techniques (iontophoresis vs. intradermal injection vs. transdermal patch), but also in the methods of the analgesia assessment, and also the differences in either the type of administered opioid drugs or their dosage.…”

Section: Discussionmentioning

confidence: 99%

“…The involvement of the skin MOR in peripheral analgesia is a matter of recent intensive research. Several studies have described the role of the skin opioid receptors in peripheral analgesia induced by various opioids in rhesus monkeys [9–11], but also most recently in humans after transcutaneous iontophoresis of methadone [12] or intradermal injections of fentanyl [13].…”

Section: Introductionmentioning

confidence: 99%

Effect of Local Administration of Transdermal Fentanyl on Peripheral Opioid Analgesia

2007

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“…Alternatively, systemic release of opioids may have indirectly sensitized peripheral nerves via inflammatory mechanisms. 13,14,23,25 Naloxone also blocked a decrease in sensitivity to heat in pain-intolerant participants at the unburnt site in the immersed hand after the immersions. As this was limited to the immersed hand, this finding is consistent with local opioid analgesia.…”

Section: Individual Differences In Tolerance Of Cold-painmentioning

confidence: 98%

The Effect of Subcutaneous Naloxone on Experimentally Induced Pain

Robertson¹,

Hammond²,

Drummond³

2008

The Journal of Pain

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Telephone+61 8 9360 2415Fax +61 8 9360 6492Keywords: opioids; thermal hyperalgesia; peripheral opioid analgesia; cold pressor; pain tolerance; pain sensitivityRunning head: opioid analgesia and hyperalgesia -2 - ABSTRACTThe heat pain threshold was assessed in 32 healthy participants after a mild burn on the dorsal surface of each hand, after injection of an opioid antagonist (80 µg naloxone) or vehicle alone (0.2 mL saline) into the burnt skin of one hand, and after repeated painful immersion of this hand in cold water for up to 180 s. We hypothesized that sensitivity to heat would decrease at the burn-injured site after the immersions, due to local release of opioids into the burnt skin.Naloxone augmented cold-induced pain during the immersions in participants who tolerated the longest immersions, implying that release of endogenous opioids suppressed cold-pain.After the immersions, sensitivity to heat decreased at the burn-injured site in the immersed hand, but naloxone did not block this effect. Instead, naloxone altered sensitivity to heat in unburnt skin, implying that thermal hyperalgesia at sites of burn injury masked the modulatory effects of opioids. In particular, naloxone blocked a decrease in sensitivity to heat at an unburnt site on the contralateral hand of participants who tolerated the longest immersions, consistent with central or systemic opioid release. Naloxone reduced sensitivity to heat at unburnt sites in participants who tolerated medium-length immersions, suggesting that an increase in systemic or central opioid activity evoked thermal hyperalgesia in this group. In addition, in a small group of participants who tolerated only brief immersions, naloxone blocked decreases in sensitivity to heat at an unburnt site in the immersed hand.These findings suggest that repeated painful immersions trigger local opioid release in participants who tolerate only brief immersions, and elicit central or systemic opioid release in participants who tolerate longer immersions.Perspective: This article demonstrates that repeated immersion of the hand in painfully cold water increases opioid activity, and that the increase in opioid activity exerts multiple opposing effects on sensitivity to heat. Individual differences in the response to opioids might contribute to individual differences in pain tolerance.

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Transcutaneous iontophoresis of methadone provokes local flushing and thermal hyperalgesia

Abstract: Stimulation of mu-opioid receptors dilated cutaneous blood vessels, and evoked local thermal analgesia and hyperalgesia at different stimulus intensities. However, stimulation of mu-opioid receptors did not produce wheals or flares.

Cited by 7 publications

References 30 publications

A New Transient Sham TENS Device Allows for Investigator Blinding While Delivering a True Placebo Treatment

A New Transient Sham TENS Device Allows for Investigator Blinding While Delivering a True Placebo Treatment

Effect of Local Administration of Transdermal Fentanyl on Peripheral Opioid Analgesia

The Effect of Subcutaneous Naloxone on Experimentally Induced Pain

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