Pain
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The treatment of neuropathic pain by neuromodulation is an objective for more than 40 years in modern clinical practice. With respect to spinal cord and deep brain structures, the cerebral cortex is the most recently evaluated target of invasive neuromodulation therapy for pain. In the early 90s, the first successes of invasive epidural motor cortex stimulation (EMCS) were published. ⋯ It is therefore important to know the principles and to assess the merit of these techniques on the basis of a rigorous assessment of the results, to avoid fad. Various types of chronic neuropathic pain syndromes can be significantly relieved by EMCS or repeated daily sessions of high-frequency (5-20 Hz) rTMS or anodal tDCS over weeks, at least when pain is lateralized and stimulation is applied to the motor cortex contralateral to pain side. However, cortical stimulation therapy remains to be optimized, especially by improving EMCS electrode design, rTMS targeting, or tDCS montage, to reduce the rate of nonresponders, who do not experience clinically relevant effects of these techniques.
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The full role of adult hippocampal neurogenesis (AHN) remains to be determined, yet it is implicated in learning and emotional functions, and is disrupted in negative mood disorders. Recent evidence indicates that AHN is decreased in persistent pain consistent with the idea that chronic pain is a major stressor, associated with negative moods and abnormal memories. Yet, the role of AHN in development of persistent pain has remained unexplored. ⋯ Downregulating neurogenesis reversibly diminished or blocked persistent pain; oppositely, upregulating neurogenesis led to prolonged persistent pain. Moreover, we could dissociate negative mood from persistent pain. These results suggest that AHN-mediated hippocampal learning mechanisms are involved in the emergence of persistent pain.
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Motor vehicle collision (MVC) can trigger chronic widespread pain (CWP) development in vulnerable individuals. Whether such CWP typically develops through the evolution of pain from regional to widespread or through the early development of widespread pain with nonrecovery is currently unknown. We evaluated the trajectory of CWP development (American College of Rheumatology criteria) among 948 European-American individuals who presented to the emergency department (ED) for care in the early aftermath of MVC. ⋯ Linear solution plots supported a nonrecovery model. Although the number of body regions with pain in the non-CWP group steadily declined, the number of body regions with pain in the CWP trajectory group (192/895, 22%) remained relatively constant over time. These data support the hypothesis that individuals who develop CWP after MVC develop widespread pain in the early aftermath of MVC, which does not remit.
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Fatty acid amide hydrolase (FAAH) metabolizes the endocannabinoid anandamide, which has an important role in nociception. We investigated the role of common FAAH single-nucleotide polymorphisms (SNPs) in experimentally induced and postoperative pain. One thousand women undergoing surgery for breast cancer participated in the study. ⋯ In conclusion, FAAH gene variation was shown to associate with cold pain sensitivity with P129T/rs324420 being the most likely causal variant as it is known to reduce the FAAH enzyme activity. The same variant showed nominal association with postoperative oxycodone consumption. Our conclusions are, however, limited by the lack of replication and the results should be replicated in an independent cohort.
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Observational Study
The relationship between overactivity and opioid use in chronic pain: a five day observational study.
With increasing concerns about the potential harm of long-term opioid therapy, there is a need for the development and implementation of alternative treatment strategies for patients with chronic pain who have been using opioids for a prolonged period of time. Based on the findings from a recent qualitative investigation that suggested there may be a bidirectional association between opioid reliance and habitual overactivity behaviour (activity engagement that significantly exacerbates pain), this study was designed to quantitatively investigate the association between opioid use and habitual overactivity over a 5-day period in a group of chronic pain patients. Participants provided a list of their prescribed pain medication, completed a self-report measure of habitual overactivity, and then commenced 5 days of data collection. ⋯ In addition, higher levels of habitual overactivity were associated with more frequent pro re nata ("as needed") opioid use over the 5 days, and with a discrepancy between the prescribed and actual oral morphine-equivalent daily dose, where more medication was taken than was prescribed. There was no predominant context for pro re nata use. The results of this study support the idea that habitual overactivity behaviour may play a role in the development of reliance on opioid medication and that such an association may provide a potential treatment target for opioid therapy rationalisation.