Pain
-
Randomized Controlled Trial
Effects of COX inhibition on experimental pain and hyperalgesia during and after remifentanil infusion in humans.
Opioids may enhance pain sensitivity resulting in opioid-induced hyperalgesia (OIH). Activation of spinal cyclooxygenase may play a role in the development of OIH. The aim of this study was to demonstrate remifentanil-induced postinfusion hyperalgesia in an electrical pain and a cold pain model, and to investigate whether COX-2 (parecoxib) or COX-1 (ketorolac) inhibition could prevent hyperalgesia after remifentanil infusion. ⋯ These results demonstrated OIH in both models, and may suggest that COX-2 inhibition is more important than COX-1 inhibition in reducing hyperalgesia. Remifentanil-induced hyperalgesia was demonstrated for both electrically induced pain and cold-pressor pain. Both parecoxib and ketorolac prevented hyperalgesia in the electrical model, parecoxib to a larger extent.
-
Electrical stimulation of the primary motor cortex has been used since 1991 to treat chronic neuropathic pain. Since its inception, motor cortex stimulation (MCS) treatment has had varied clinical outcomes. Until this point, there has not been a systematic study of the stimulation parameters that most effectively treat chronic pain, or of the mechanisms by which MCS relieves pain. ⋯ We also find that stimulation of the ZI mimics the effects of MCS and that reversible inactivation of ZI blocks the effects of MCS. These findings suggest that the reduction of hyperalgesia may be due to MCS effects on ZI. In an animal model of central pain syndrome, motor cortex stimulation reduces hyperalgesia by activating zona incerta and therefore restoring inhibition in the thalamus.
-
The benefits of transcutaneous electrical nerve stimulation (TENS) for pain relief have not been reliably established, as most systematic reviews find poor methodological quality in many studies. The paradox within the evidence base for TENS is that despite identified sources of bias that may lead to an overestimation of treatment effects, no benefits for TENS can be clearly demonstrated. Conventional assessments of quality assume a single direction of bias, and little work has been undertaken examining other directions of bias. ⋯ We propose criteria for judging directions of bias in future studies of TENS that may be adapted to assess other trials in which implementation fidelity is important, such as other nonpharmacological interventions for pain. Poor implementation fidelity was identified as a significant source of bias in systematic reviews of TENS studies and might explain lack of consistent treatment effects of TENS in pain. Here, criteria for assessing methodology are proposed for use in designing future clinical trials of TENS.
-
Given the previous evidence for involvement of prostanoid EP1 receptors in facilitation of the bladder afferent nerve activity and micturition reflex, the present study investigated the effect of ONO-8130, a selective EP1 receptor antagonist, on cystitis-related bladder pain in mice. Cystitis in mice was produced by intraperitoneal administration of cyclophosphamide at 300mg/kg. Bladder pain-like nociceptive behavior and referred hyperalgesia were assessed in conscious mice. ⋯ Intravesical administration of prostaglandin E2 caused prompt phosphorylation of ERK in the L6 spinal cord, an effect blocked by ONO-8130. Our findings strongly suggest that the prostaglandin E2/EP1 system participates in processing of cystitis-related bladder pain, and that EP1 antagonists including ONO-8130 are useful for treatment of bladder pain, particularly in interstitial cystitis. Prostaglandin E2 contributes to cystitis-related bladder pain via EP1 receptors in mice, indicating possible therapeutic usefulness of selective EP1 antagonists.