European journal of pain : EJP
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Randomized Controlled Trial Clinical Trial
Effect of muscle relaxants on experimental jaw-muscle pain and jaw-stretch reflexes: a double-blind and placebo-controlled trial.
A randomised, double-blind, placebo-controlled three-way cross-over study was performed to investigate the effect of two muscle relaxants (tolperisone hydrochloride and pridinol mesilate) on experimental jaw-muscle pain and jaw-stretch reflexes. Fifteen healthy men participated in three randomised sessions separated by at least 1 week. In each session 300 mg tolperisone, 8 mg pridinol mesilate or placebo was administered orally as a single dose. ⋯ Administration of pridinol mesilate was associated with a significant decrease in PPTs compared with tolperisone hydrochloride and placebo (P=0.002) after medication, but not after experimental jaw-muscle pain. The normalised peak-to-peak amplitude of the stretch reflexes were not significantly influenced by the test medication (P=0.762), but were in all sessions significantly facilitated during ongoing experimental jaw-muscle pain (P=0.034). In conclusion, tolperisone hydrochloride provides a small, albeit significant reduction in the perceived intensity of experimental jaw-muscle pain whereas the present dose had no effect on the short-latency jaw-stretch reflex.
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While morphine is historically the gold standard for the management of severe cancer pain, some patients either do not achieve adequate analgesia, or suffer intolerable side-effects. For these patients an alternative opioid is recommended. ⋯ Similar to morphine, transdermal fentanyl is effective for the management of moderate to severe cancer pain. However, inappropriate prescribing of transdermal fentanyl, particularly in the clinical setting of unstable pain, can cause significant opioid toxicity, as highlighted in the case reports described.
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The effects of the S enantiomer of RB101, a complete inhibitor of enkephalin-catabolizing enzymes, alone or in combination with a functional NMDA receptor antagonist, (+)-HA966 were studied on the spinal c-Fos protein expression in the carrageenan model of inflammatory nociception. One hour 30min after intraplantar carrageenan in awake rats, c-Fos immunoreactive (c-Fos-IR) nuclei were preferentially located in the laminae I-II and V-VI of the spinal dorsal horn, i.e., spinal areas containing numerous neurons responding exclusively, or not, to peripheral nociceptive stimuli. RB101(S) (5, 10, 20 and 40mg/kg i.v.) dose-dependently reduced the total number of carrageenan-evoked c-Fos-IR nuclei (r=0.63, P<0.01), with 49+/-3% reduction (P<0.001) for the highest dose. ⋯ These effects were partially reversed by naloxone. These results provide evidence for the potent effects of combination of RB101(S) and (+)-HA966. Considering the absence of major opioid side effects of RB101(S) and the marked increase of its antinociceptive effects by NMDA receptor antagonist, this type of drug combination could have beneficial therapeutical application.
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Factors influencing the features of postherpetic neuralgia and outcome when treated with tricyclics.
This paper retrospectively reviews features of postherpetic neuralgia (PHN) in up to 279 personal patients in relation to treatment outcome when treated with tricyclic antidepressants (TCAs). Factors affecting characteristics of PHN: (i) Patients with allodynia (89%) and/or burning pain (56%) have a much higher visual analogue pain intensity score than those without; (ii) Acyclovir (ACV) given for acute shingles (HZ) does not reduce the incidence of subsequent PHN, but reduces the pain intensity in PHN patients with allodynia; (iii) ACV given for acute HZ reduces the incidence of burning pain in subsequent PHN, but not of allodynia; (iv) ACV given for acute HZ reduces the incidence of clinically detectable sensory deficit in subsequent PHN. Factors affecting outcome of TCA-treated PHN: (i) The point in time at which TCA treatment is commenced is by far the most critical factor: started between 3 and 12 months after acute HZ onset, more than two-thirds obtain pain relief (NNT=1.8); between 13 and 24 months, two-fifths (41%) (NNT=3.6); and more than two years, one-third (NNT=8.3). Background and paroxysmal pain disappear earlier and are more susceptible of relief than allodynia. (ii) Twice as many (86%) of PHN patients without allodynia obtain pain relief with TCA treatment than those with (42%); (iii) the use of ACV for acute HZ more than halves the time-to-relief of PHN patients by TCAs; (iv) PHN patients with burning pain are significantly less likely to obtain pain relief with TCAs than those without (p<0.0001).
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Deep tissue pain can be related to reduced muscle blood flow, which comprises the metabolic demand under muscle work. The tissues and receptors involved in nociception after ischaemic muscle contractions are not known. The concentration of adenosine is increased after ischaemic contractions and might act as an algesic substance. ⋯ During hypertonic saline infusions, the pressure pain threshold was decreased compared with before and immediately after the pain had vanished. The present study shows that pharmacological levels of adenosine in skeletal muscle did not induce pain. Excitation of muscle nociceptors by hypertonic saline evoked hyperalgesia, larger areas of pain, and a different quality of pain compared with ischaemic contractions, suggesting that the pain after ischaemic contractions is mediated by other populations of nociceptors in muscle and/or other tissues than excited by hypertonic saline.