Pain
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Randomized Controlled Trial Multicenter Study
Systemic effects of epidural steroid injections for spinal stenosis.
This analysis of the lumbar epidural steroid injections for spinal stenosis multicenter randomized controlled trial data identifies the degree of and risk factors for cortisol suppression after epidural steroid injections in older adults with spinal stenosis. Four hundred patients aged 50 years and older with back or leg pain and central lumbar spinal stenosis completed baseline demographic and psychosocial measures. Morning serum cortisol levels were measured at baseline and 3 weeks after initial injection. ⋯ The effect on 3-week cortisol changes did not differ by demographic or patient-level characteristics. Those treated with methylprednisolone or triamcinolone had an average 3-week cortisol reduction of 41.0% (P = 0.005) and 41.6% (P < 0.001) from baseline, respectively, whereas patients treated with betamethasone or dexamethasone were not significantly different than comparable patients in the lidocaine arm. The higher rates of cortisol suppression at 3 weeks in those receiving epidural corticosteroid injections, particularly with longer-acting insoluble corticosteroid formulations, are consistent with sustained systemic absorption of corticosteroid.
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Randomized Controlled Trial
Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study.
The long-term safety of naldemedine, a peripherally acting µ-opioid receptor antagonist, was evaluated in patients with opioid-induced constipation and chronic noncancer pain in a 52-week, randomized, double-blind, phase 3 study. Eligible adults who could be on a routine laxative regimen were randomized 1:1 to receive once-daily oral naldemedine 0.2 mg (n = 623) or placebo (n = 623). The primary endpoint was summary measures of treatment-emergent adverse events (AEs). ⋯ Sustained significant improvements in bowel movement frequency and overall constipation-related symptoms and quality of life were observed with naldemedine (P ≤ 0.0001 vs placebo at all time points). Naldemedine was generally well tolerated for 52 weeks and did not interfere with opioid-mediated analgesia or precipitate opioid withdrawal. Naldemedine significantly increased bowel movement frequency, improved symptomatic burden of opioid-induced constipation, and increased patients' quality of life vs placebo.
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The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. ⋯ Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.
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Chronic postsurgical pain (CPSP) is a well-recognized potential complication with negative personal, social, and health care consequences. However, limited data exist on CPSP and on the course of pain over time after hysterectomy. Using data from a prospective cohort study on a consecutive sample assessed at 4 time points, presurgery (T1), 48 hours (T2), 4 months (T3), and 5 years postsurgery (T4), we sought to examine women's PSP trajectories using assessments of pain at T3 and T4. ⋯ Membership in PT2 and PT3 was predicted by presurgical anxiety (odds ratio [OR] = 1.131, P = 0.015; OR = 1.175, P = 0.009, respectively), emotional representation of the surgical disease (OR = 1.155, P = 0.034; OR = 1.213, P = 0.020, respectively), and pain catastrophizing (OR = 1.079, P = 0.043; OR = 1.143, P = 0.001, respectively). Furthermore, acute PSP intensity and frequency determined membership of women in PT3 (OR = 1.211, P = 0.033; OR = 3.000, P = 0.029, respectively), and postsurgical anxiety (OR = 1.182, P = 0.026) also played a key predictive role. This study identified factors that can be easily screened before and after surgery and are amenable to change through carefully designed timely and tailored interventions for women at risk of an unfavorable PSP trajectory posthysterectomy.