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Dysfunction of the prefrontal-hippocampal circuit has been identified as a leading cause to pain-related working-memory (WM) deficits. However, the underlying mechanisms remain poorly determined. To address this issue, we implanted multichannel arrays of electrodes in the prelimbic cortex (PL-mPFC), and in the dorsal hippocampal CA1 field (dCA1) to record the neural activity during the performance of a delayed non-match to sample (DNMS) task. The prefrontal-hippocampal connectivity was selectively modulated by bidirectional optogenetic inhibition or stimulation of local PL-mPFC glutamatergic calcium/calmodulin-dependent protein kinase-II alpha (CaMKIIα) expressing neurons during the DNMS task delay-period. The within-subject behavioral performance was assessed using a persistent neuropathic pain model – spared nerve injury (SNI). Our results showed that the induction of the neuropathic pain condition affects the interplay between PL-mPFC and dCA1 regions in a frequency-dependent manner, and that occurs particularly across theta oscillations while rats performed the task. In SNI-treated rats, this disruption was reversed by the selective optogenetic inhibition of PL-mPFC CaMKIIα-expressing neurons during the last portion of the delay-period, but without any significant effect on pain responses. Finally, we found that prefrontal-hippocampal theta connectivity is strictly associated with higher performance levels. Together, our findings suggest that PL-mPFC CaMKIIα-expressing neurons could be modulated by painful conditions and their activity may be critical for prefrontal-hippocampal connectivity during WM processing.
Learn More >To provide an overview of current interventional pain management techniques for primary headaches with a focus on peripheral nerve stimulation and nerve blocks.
Learn More >While clinicians have been using antidepressants for off-label indications in the treatment of chronic pain in recent years, newer studies have proven effectiveness and provided additional mechanistic understanding and defined potential adverse effects. As depression and chronic pain are frequently comorbid conditions, the use of antidepressants has allowed for treatment of both conditions concomitantly in the same patient population.
Learn More >Traumatic brain injury (TBI) is a major public health concern in the USA and worldwide. Sleep disruption and headaches are two of the most common problems reported by patients after TBI. In this manuscript, we review the current knowledge regarding the relation between post-traumatic sleep disruption and headaches. We also describe the role of the glymphatic system as a potential link between TBI, sleep, and headaches.
Learn More >Phantom sensations are incompletely understood phenomena which take place following an amputation or deafferentation of a limb. They can present as kinetic, kinesthetic, or exteroceptive perceptions. It is estimated that phantom limb pain (PLP) affects anywhere from 40 to 80% of amputees.
Learn More >Pain is the most characteristic feature of sickle cell disease (SCD). Patients with SCD live with unpredictable, recurrent episodes of acute painful crisis, as well as chronic unremitting pain throughout their lifetime. While most of the research and medical efforts have focused on treating vaso-occlusion crisis and acute pain, chronic pain remains a significant challenge faced by patients and physicians. Emerging evidence from human and animal studies has suggested the presence of a neuropathic component in SCD pain. New knowledge on the neurobiology of chronic pain in SCD has significant implications in unraveling the underlying mechanisms. This review focuses on the recent advances on the role of protein kinase C or PKC in promoting and maintaining chronic pain conditions. With a highlight of a specific PKC isoform, PKCδ, we aim to propose PKC as an essential regulator of chronic pain in SCD, which may ultimately lead to innovative therapeutic strategies for treating this devastating life-long problem in patients with SCD.
Learn More >Background and aims Chronic pain after traumatic injury and surgery is highly prevalent, and associated with substantial psychosocial co-morbidities and prolonged opioid use. It is currently unclear whether predicting chronic post-injury pain is possible. If so, it is unclear if predicting chronic post-injury pain requires a comprehensive set of variables or can be achieved only with data available from the electronic medical records. In this prospective study, we examined models to predict pain at the site of injury 3-6 months after hospital discharge among adult patients after major traumatic injury requiring surgery. Two models were developed: one with a comprehensive set of predictors and one based only on variables available in the electronic medical records. Methods We examined pre-injury and post-injury clinical variables, and clinical management of pain. Patients were interviewed to assess chronic pain, defined as the presence of pain at the site of injury. Prediction models were developed using forward stepwise regression, using follow-up surveys at 3-6 months. Potential predictors identified a priori were: age; sex; presence of pre-existing chronic pain; intensity of post-operative pain at 6 h; in-hospital opioid consumption; injury severity score (ISS); location of trauma, defined as body region; use of regional analgesia intra- and/or post-operatively; pre-trauma PROMIS Depression, Physical Function, and Anxiety scores; in-hospital Widespread Pain Index and Symptom Severity Score; and number of post-operative non-opioid medications. After the final model was developed, a reduced model, based only on variables available in the electronic medical record was run to understand the "value add" of variables taken from study-specific instruments. Results Of 173 patients who completed the baseline interview, 112 completed the follow-up within 3-6 months. The prevalence of chronic pain was 66%. Opioid use increased from 16% pre-injury to 28% at 3-6 months. The final model included six variables, from an initial set of 24 potential predictors. The apparent area under the ROC curve (AUROC) of 0.78 for predicting pain 3-6 months was optimism-corrected to 0.73. The reduced final model, using only data available from the electronic health records, included post-surgical pain score at 6 h, presence of a head injury, use of regional analgesia, and the number of post-operative non-opioid medications used for pain relief. This reduced model had an apparent AUROC of 0.76, optimism-corrected to 0.72. Conclusions Pain 3-6 months after trauma and surgery is highly prevalent and associated with an increase in opioid use. Chronic pain at the site of injury at 3-6 months after trauma and surgery may be predicted during hospitalization by using routinely collected clinical data. Implications If our model is validated in other populations, it would provide a tool that can be easily implemented by any provider with access to medical records. Patients at risk of developing chronic pain could be selected for studies on preventive strategies, thereby concentrating the interventions to patients who are most likely to transition to chronic pain.
Learn More >Although chronic pain after amputation is frequent, the underlying mechanisms are still not well understood. It is widely accepted that the pathogenesis of postamputation pain is multifactorial, with both peripheral and central mechanisms playing an essential role. However, recent studies suggest that the immune system plays an important role in different neuropathic pain conditions, including postamputation pain. Eleven amputees were included in this clinical study. Information on the type and intensity of spontaneous postamputation pain was obtained and evoked pain responses for brush, cold, and warm allodynia and pinprick hyperalgesia were determined. In addition, skin biopsies were taken from the amputated site and a contralateral control site and analysed for possible markers of pain: IbA1 (macrophages), calcitonin gene-related peptide (CGRP), and substance P (SP). Irrespectively of the type and intensity of postamputation pain, no differences were found in IbA1, CGRP, and SP levels between the amputated site and the control site. Although no differences between the sites were seen in this study, this new method seems promising for our understanding of skin changes in amputees. In future studies, staining for other cytokines and inflammatory mediators in skin biopsies could provide new insight into the mechanisms of postamputation pain.
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