Pain
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Randomized Controlled Trial Multicenter Study
Intrathecal delivery of hydromorphone vs morphine for refractory cancer pain: a multicenter, randomized, single-blind, controlled noninferiority trial.
Hydromorphone is an alternative to morphine for intrathecal drug delivery system to treat refractory cancer pain; however, there is not enough clinical evidence to prove it. In our study, 233 patients from 12 different pain management centers across China were enrolled, 121 and 112 in the intrathecal hydromorphone (ITHM) and intrathecal morphine (ITMO) groups, respectively. The primary outcome was the clinical success rate, which was defined as ratio of patients achieving ≥50% pain relief. ⋯ The patient-controlled analgesia bolus change rate was lower in the ITHM group than in the ITMO group (ITHM -19.88% vs ITMO 7.79%, P < 0.01, t test) from first week. Our result shows that ITHM is noninferior to ITMO on pain relief to treat refractory cancer pain, however, at different doses and that the doses of morphine tended to increase, whereas those of hydromorphone decreased over time. Hydromorphone offers advantage over morphine in controlling BTP.
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Randomized Controlled Trial
Acupuncture of different treatment frequency in knee osteoarthritis: a pilot randomised controlled trial.
This 16-week randomised controlled trial (8-week treatment followed by 8-week follow-up) evaluated the symptomatic improvement in patients with knee osteoarthritis on 3 sessions per week of acupuncture (TSWA) compared to 1 session per week of acupuncture (OSWA). Sixty participants were randomised to either the TSWA or the OSWA group in a 1:1 ratio. The primary outcome was response rate, defined as the percentage of participants achieving ≥2 points decrease on the numerical rating scale (NRS) and ≥6 points decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. ⋯ There were no significant between-group differences in WOMAC stiffness and SF-12. In summary, TSWA immediately improved knee pain and dysfunction compared with OSWA. In addition, the benefit of TSWA persists throughout follow-up.
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The voltage-gated calcium channels CaV3.1-3.3 constitute the T-type subfamily, whose dysfunctions are associated with epilepsy, psychiatric disorders, and chronic pain. The unique properties of low-voltage-activation, faster inactivation, and slower deactivation of these channels support their role in modulation of cellular excitability and low-threshold firing. Thus, selective T-type calcium channel antagonists are highly sought after. ⋯ High voltage-gated calcium, as well as tetrodotoxin-sensitive and -resistant sodium, channels were unaffected by 5bk. 5bk inhibited spontaneous excitatory postsynaptic currents and depolarization-evoked release of calcitonin gene-related peptide from lumbar spinal cord slices. Notably, 5bk did not bind human mu, delta, or kappa opioid receptors. 5bk reversed mechanical allodynia in rat models of HIV-associated neuropathy, chemotherapy-induced peripheral neuropathy, and spinal nerve ligation-induced neuropathy, without effects on locomotion or anxiety. Thus, 5bk represents a novel T-type modulator that could be used to develop nonaddictive pain therapeutics.
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Migraine is one of the most disabling disorders worldwide but the underlying mechanisms are poorly understood. Stress is consistently reported as a common trigger of migraine attacks. Here, we show that repeated stress in mice causes migraine-like behaviors that are responsive to a migraine therapeutic. ⋯ Finally, mice received either the calcitonin gene-related peptide monoclonal antibody ALD405 (10 mg/kg) 24 hours before SNP or a coinjection of sumatriptan (0.6 mg/kg). ALD405, but not sumatriptan, blocked the facial hypersensitivity due to SNP. This stress paradigm in mice and the subsequent primed state caused by stress allow further preclinical investigation of mechanisms contributing to migraine, particularly those caused by common triggers of attacks.
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No externally validated presurgical risk score for chronic postsurgical pain (CPSP) is currently available. We tested the generalizability of a six-factor risk model for CPSP developed from a prospective cohort of 2929 patients in 4 surgical settings. Seventeen centers enrolled 1225 patients scheduled for inguinal hernia repair, hysterectomy (vaginal or abdominal), or thoracotomy. ⋯ The c-statistics (95% confidence interval) were similar in the full validation sample and the 2 subsamples: 0.69 (0.65-0.73), 0.69 (0.63-0.74), and 0.68 (0.63-0.74), respectively. Calibration was good (slope b and intercept close to 1 and 0, respectively, and nonsignificance in the Hosmer-Lemeshow goodness-of-fit test). The validated model based on 6 clinical factors reliably identifies risk for CPSP risk in about 70% of patients undergoing the surgeries studied, allowing surgeons and anesthesiologists to plan and initiate risk-reduction strategies in routine practice and researchers to screen for risk when randomizing patients in trials.