Lumbar epidural fentanyl: segmental spread and effect on temporal summation and muscle pain

Background. Despite extensive use, different aspects of the pharmacological action of epidural fentanyl have not been clarified. We applied a multi‐modal sensory test procedure to investigate the effect of epidural fentanyl on segmental spread, temporal summation (as a measure for short‐lasting central hyperexcitability) and muscle pain. Methods. Thirty patients received either placebo, 50 or 100 µg single dose of fentanyl epidurally (L2-3), in a randomized, double‐blind fashion. Heat pain tolerance thresholds at eight dermatomes from S1 to fifth cranial nerve (assessment of segmental spread), pain threshold to transcutaneous repeated electrical stimulation of the sural nerve (assessment of temporal summation) and pain intensity after injection of hypertonic saline into the tibialis anterior muscle (assessment of muscle pain) were recorded. Results. Fentanyl 100 µg, but not 50 µg, produced analgesia to heat stimulation only at L2. Surprisingly, no effect at S1 was detected. Both fentanyl doses significantly increased temporal summation threshold and decreased muscle pain intensity. Conclusions. The findings suggest that a single lumbar epidural dose of fentanyl should be injected at the spinal interspace corresponding to the dermatomal site of pain. Increased effect on L2 compared with S1 suggests that drug effect on spinal nerve roots and binding to opioid receptors on the dorsal root ganglia may be more important than traditionally believed for the segmental effect of epidurally injected fentanyl. Epidural fentanyl increases temporal summation threshold and could therefore contribute to prevention and treatment of central hypersensitivity states. I.M. injection of hypertonic saline is a sensitive technique for detecting the analgesic action of epidural opioids. Br J Anaesth 2003; 90: 467-7

Functional and Structural Neuroplastic Changes Related to Sensitization Proxies in Patients with Osteoarthritis: A Systematic Review

Objective: Several reports in literature have identified sensitization as a possible basis for the enhanced pain reactions associated with osteoarthritis (OA). The aim of this current systematic review is to summarize functional and structural brain changes associated with surrogate sensitization parameters assessed in patients with OA-related pain. Design: Systematic review. Subjects: Patients with OA related pain. Methods: A literature search was conducted systematically in MEDLINE, CINAHL, EMBASE databases for human studies up to December 2019. Articles were included if they assessed brain imaging and sensitization parameters (quantitative sensory testing and questionnaires) in adults with OA-related pain. Methodological quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) score. Results: Five studies reporting on 138 patients were included in this review. The MINORS scale yielded mean scores of 8.5/16 and 12.3/24, for the cohort and case-control studies respectively. Four low-quality studies suggest a greater pain matrix activation associated with clinical measures of sensitization in patients with OA, while another study underlined the presence of structural changes (reduced gray matter volume) in the cortical areas involved in the nociceptive processing possible also related to sensitization. Conclusions: This review shows conflicting evidence for structural and functional neuroplastic brain changes related to sensitization proxies in patients with OA

Ondansetron does not inhibit the analgesic effect of alfentanil

5-Hydroxytryptamine (5-HT) causes antinociception via presynaptic 5-HT3 (5-HT subtype 3) receptors on primary afferent nociceptive neurones in the spinal cord dorsal horn. Therefore, ondansetron (a 5-HT3 receptor antagonist) may increase the perception of a noxious stimulus or decrease the effects of concurrently administered antinociceptive drugs. Using a randomized, doubleblind, crossover study design, we have tested this hypothesis in eight healthy volunteers who, on three different days, received either ondansetron and placebo, ondansetron and alfentanil or placebo and alfentanil. Experimental pain was induced with heat, cold, mechanical pressure and electrical stimulation. Ondansetron alone did not change the response to any of the experimental tests, but alfentanil and the combination ondansetron- alfentanil significantly changed the response compared with ondansetron alone. There was no difference between alfentanil alone and the combination ondansetron-alfentanil. We conclude that ondansetron does not change the response to pressure, heat, cold or electrical nociceptive stimuli or antagonize the analgesic effect of alfentani