Pain
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Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of cancer treatment that significantly compromises quality of life of cancer patients and survivors. Identification of targets for pharmacological intervention to prevent or reverse CIPN is needed. We investigated exchange protein regulated by cAMP (Epac) as a potential target. ⋯ Ex vivo, ESI-09 blocked paclitaxel-induced abnormal spontaneous discharges in dorsal root ganglion neurons. Collectively, these findings implicate Epac1 in nociceptors as a novel target for treatment of CIPN. This is clinically relevant because ESI-09 has the potential to reverse a debilitating and long-lasting side effect of cancer treatment.
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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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Neuropathic pain (NP) is an increasingly common chronic pain state and a major health burden, affecting approximately 7% to 10% of the general population. Emerging evidence suggests that genetic factors could partially explain individual susceptibility to NP and the estimated heritability in twins is 37%. The aim of this study was to systematically review and summarize the studies in humans that have investigated the influence of genetic factors associated with NP. ⋯ These findings demonstrate an important and specific contribution of genetic factors to the risk of developing NP. However, large-scale replication studies are required to validate these candidate genes. Our review also highlights the need for genome-wide association studies with consistent case definition to elucidate the genetic architecture underpinning NP.