Central hyperexcitability as measured with nociceptive flexor reflex threshold in chronic musculoskeletal pain: a systematic review.
Chronic musculoskeletal conditions are increasingly conceived as involving altered central nervous system processing, and impaired nociceptive flexor reflex (NFR) appears to reflect altered central nervous system processing. The primary objective was to synthesize the evidence for impaired NFR in these conditions. The secondary objective was to evaluate the NFR stimuli parameters employed by reviewed studies. ⋯ The results indicate that there is evidence of central hyperexcitability in people with chronic musculoskeletal pain. Our review also suggests that shorter inter-pulse duration tends to yield smaller variability in NFR threshold. However, further research investigating optimal stimulation parameters is still warranted.
Comparative mortality among Department of Veterans Affairs patients prescribed methadone or long-acting morphine for chronic pain.
Data on comparative safety of opioid analgesics are limited, but some reports suggest disproportionate mortality risk associated with methadone. Our objective was to compare mortality rates among patients who received prescribed methadone or long-acting morphine for pain. This is a retrospective observational cohort drawn from Department of Veterans Affairs (VA) health care databases, January 1, 2000, to December 31, 2007. ⋯ Multiple sensitivity analyses found either no difference in mortality between methadone and long-acting morphine or lower mortality rates among patients who received methadone. In summary, we found no evidence of excess all-cause mortality among VA patients who received methadone compared with those who received long-acting morphine. Randomized trials and prospective observational research are needed to better understand the relative safety of long-acting opioids.
Review Meta Analysis
Systematic review of movement-evoked pain versus pain at rest in postsurgical clinical trials and meta-analyses: a fundamental distinction requiring standardized measurement.
To estimate frequency of movement-evoked pain (MEP) measurement in human postsurgical investigations, we reviewed thoracotomy, knee arthroplasty, and hysterectomy clinical trials and meta-analyses. Only 39% of trials measured MEP and 52% failed to identify pain outcome as pain at rest (PAR) or MEP. Temporal trending did not suggest that MEP measurement is becoming more frequent. ⋯ This is an important problem because MEP is usually more severe than PAR; MEP exerts a more direct adverse impact on postsurgical functional recovery and several current and novel pain treatments differentially affect MEP vs PAR. Failure to distinguish between PAR and MEP and standardize their measurement threatens trial precision and ability to identify interventions with the most clinically relevant effects on pain. We therefore recommend developing consistent terminology regarding PAR and MEP, considering inclusion of MEP as a pain outcome in every postsurgical trial, and standardizing measurement of PAR and MEP on a procedure-specific basis.
Prescription opioid analgesics rapidly change the human brain.
Chronic opioid exposure is known to produce neuroplastic changes in animals; however, it is not known if opioids used over short periods of time and at analgesic dosages can similarly change brain structure in humans. In this longitudinal, magnetic resonance imaging study, 10 individuals with chronic low back pain were administered oral morphine daily for 1 month. High-resolution anatomical images of the brain were acquired immediately before and after the morphine administration period. ⋯ The results add to a growing body of literature showing that opioid exposure causes structural and functional changes in reward- and affect-processing circuitry. Morphologic changes occur rapidly in humans during new exposure to prescription opioid analgesics. Further research is needed to determine the clinical impact of those opioid-induced gray matter changes.
Stress-induced hyperalgesia is associated with a reduced and delayed GABA inhibitory control that enhances post-synaptic NMDA receptor activation in the spinal cord.
GABA and glutamate are both affected by stress and are involved in nociception. Thus, we determined whether stress-induced enhancement of inflammatory hyperalgesia is mediated by an imbalance between glutamate and GABA neurotransmission. Male rats were subjected daily to 10 to 20 minutes per day of either forced swimming (FS) or sham swimming for 3 consecutive days; nonconditioned rats served as controls. ⋯ Diazepam effects were blocked by flumazenil. NO(x) increased in lumbar spinal cord of FS rats by a mechanism antagonized by ketamine. Thus, stress-induced hyperalgesia is initiated by a decreased and delayed GABA release and GABA-A receptor activation, whereas it is maintained by increased glutamate release and NMDA glutamate receptor activation at the spinal level.