Neuroscience
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Chronic low back pain (CLBP) is challenging to treat. Minimal invasive neurostimulation therapies, such as subcutaneous peripheral nerve field stimulation (SPNS), improve pain relief and quality of life. The goal of the present study was to assess the usefulness, safety, and efficacy of SPNS in patients with CLBP. ⋯ The complication rate was 23% (3/13 patients). In non-responders, VAS and ODI at 24 months dropped significantly as well but the decrease was less pronounced compared to responders and had not led to a decrease in pain medication. SPNS is a novel, safe, and effective treatment for CLBP and may have advantages over interventional treatments including intrathecal therapy and spinal cord stimulation.
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Although bone is continually being remodeled and ultimately declines with aging, little is known whether similar changes occur in the sensory and sympathetic nerve fibers that innervate bone. Here, immunohistochemistry and confocal microscopy were used to examine changes in the sensory and sympathetic nerve fibers that innervate the young (10 days post-partum), adult (3 months) and aging (24 months) C57Bl/6 mouse femur. In all three ages examined, the periosteum was the most densely innervated bone compartment. ⋯ In cortical bone, sensory and sympathetic nerve fibers are largely confined to vascularized Haversian canals and while there is no significant decline in the density of sensory fibers, there was a 75% reduction in sympathetic nerve fibers in the aging vs. adult cortical bone. In contrast, in the bone marrow the overall density/unit area of both sensory and sympathetic nerve fibers appeared to remain largely unchanged across the lifespan. The preferential preservation of sensory nerve fibers suggests that even as bone itself undergoes a marked decline with age, the nociceptors that detect injury and signal skeletal pain remain relatively intact.
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Neonatal pain has been suggested to contribute to the development and/or persistence of adult pain. Observations from animal models have shown that neonatal inflammation produces long-term changes in sensory neuron function, which can affect the susceptibility of adults to develop persistent pain. We used a preclinical model of transition to chronic pain, hyperalgesic priming, in which a previous inflammatory stimulus triggers a long-lasting increase in responsiveness to pro-algesic mediators, prototypically prostaglandin E2 (PGE2), to investigate if post-natal age influences susceptibility of adult rats to develop chronic pain. ⋯ In contrast, in females treated with TNFα at post-natal week 1, 2, 3, or 4, but not at 5 or 7, priming was present. This age and sex difference in the susceptibility to priming was estrogen-dependent, since injection of TNFα in 3-week-old males and 5-week-old females, in the presence of the estrogen receptor antagonist ICI 182,780, did produce priming. These results suggest that estrogen levels, which vary differently in males and females over the post-natal period, until they stabilize after puberty, impact pain as an adult.
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Neuropathic pain affects multiple brain functions, including motivational processing. However, little is known about the structural and functional brain changes involved in the transition from an acute to a chronic pain state. Here we combined behavioral phenotyping of pain thresholds with multimodal neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. ⋯ Similarly, all global and local network changes that occurred following pain induction disappeared over time, with two notable exceptions: the nucleus accumbens, which played a more dominant role in the global network in a chronic pain state and the prefrontal cortex and hippocampus, which showed lower connectivity. These changes in connectivity were accompanied by enhanced glutamate levels in the hippocampus, but not in the prefrontal cortex. We suggest that hippocampal hyperexcitability may contribute to alterations in synaptic plasticity within the nucleus accumbens, and to pain chronification.