Pain
-
Randomized Controlled Trial Clinical Trial
Analgesic profile of peroral and topical ketoprofen upon low pH-induced muscle pain.
Topical analgesics are widely marketed for treatment of muscle and joint pain. We have recently developed a model of muscle pain and have used this model to evaluate the efficacy of commercially available topical and peroral ketoprofen in order to evaluate the time- and dose-dependence of analgesia. In the present study, we examined the dose- (0, 50, and 100 mg) and time-dependence (hourly to 8 h) of commercially available peroral and topical ketoprofen. ⋯ The apparent analgesia was rapid to develop but transient and pain ratings increased back to baseline values within 3 h for the 100 mg dose and within 2 h for the 50 mg dose. This data suggests that topical application of commercial gel-based systems does not provide long-lasting analgesia in the muscle when compared to perorally-dosed ketoprofen. In addition, the data show that even doses of 100 mg peroral ketoprofen do not provide complete relief of muscle pain.
-
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal illnesses and is characterized by altered visceral perception. Previous studies in IBS have failed to demonstrate altered somatic or cutaneous perception. The aims of the study were to determine whether IBS patients have visceral hypersensitivity and cutaneous heat-induced hyperalgesia restricted to lumbosacral dermatomes, consistent with a localized segmental mechanism. ⋯ However, they did not differ from controls on several personality trait measures. These results suggest that patients with IBS have visceral hyperalgesia and cutaneous hyperalgesia that is distributed over a considerable rostral-caudal distance yet optimally expressed in lumbosacral dermatomes. This distribution is consistent with patterns of spinal hyperexcitability observed in experimentally induced persistent pain conditions.
-
We examined the effects of amlodipine, a selective L-type voltage dependent Ca(2+) channel (VDCC) blocker, and mibefradil, a selective T-type VDCC blocker on the antinociceptive effects of morphine, and mu, delta and kappa opioid receptor selective agonist-induced antinociception at the spinal level. Intrathecally administered amlodipine and mibefradil potentiated morphine and [D-Ala(2), N mePhe(4), Gly-ol(5)] enkephalin (DAMGO)-induced antinociception by shifting their dose response curves to the left. ⋯ These data indicate that L-type and T-type VDCC blockers synergistically potentiate the analgesic effects of mu opioid receptor agonists, but not delta and kappa opioid receptor agonists, at the spinal level. Additionally, these data suggest that there is an important functional interaction between L-type and/ or T-type VDCC and mu opioid receptors in the process of analgesia.
-
It has been suggested that there is a significant upregulation of the NK1 receptor (NK1R) on neurons in the dorsal spinal cord after long-term somatic inflammation. This upregulation appears to play a significant role in central sensitization in chronic pain states. However, it is not clear whether such a change is also observed after chronic visceral (bladder) inflammation. ⋯ In the L6 spinal segment, CPA-treatment enhanced NK1R immunostaining in the medial and the lateral dorsal horn, as well as in the lateral laminae including the sacral parasympathetic nucleus to a lesser extent. In CPA-treated animals, substance P staining intensity increased in the same regions in which NK1R immunoreactivity was increased. This finding probably implies the upregulation of spinal NK1R and the occurrence of central sensitization within the spinal cord after chronic visceral inflammation.
-
The present study (1) examined analgesic effects of systemically and spinally administered antidepressants (ADs) on phase 2 flinching and biting/licking behaviours in the rat formalin test, a model considered to be of greater relevance to clinical pain than acute threshold tests, and (2) determined whether motor or anti-inflammatory effects contributed to such actions. Systemic administration of amitriptyline (3-20 mg/kg) produced a dose-related enhancement of flinching behaviours, while at the same time suppressing biting/licking behaviours. Imipramine (except for 20 mg/kg), nortriptyline, desipramine and fluoxetine had no significant effect on flinching behaviours, while producing a dose-related suppression of biting/licking behaviours. ⋯ Spinal administration of nortriptyline by lumbar puncture also reduced paw volume, but for other agents, the reduction was not significant. Motor effects were noted qualitatively throughout these experiments, and considered in relation to nociceptive behaviours. These results indicate (a) a marked dissociation between the effects of systemic ADs on flinching and biting/licking behaviours in the formalin test, (b) spinal efficacy of ADs that essentially reproduces effects seen with systemic administration when given by lumbar puncture, (c) a lack of causality between anti-inflammatory effects of ADs and their analgesic properties in the formalin test, and (d) a contribution of motor effects to analgesic actions at higher doses affecting biting/licking but not flinching behaviours.