The journal of pain : official journal of the American Pain Society
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Spinal cord injury (SCI)-induced neuropathic pain (SCI-NP) develops in up to 60 to 70% of people affected by traumatic SCI, leading to a major decline in quality of life and increased risk for depression, anxiety, and addiction. Gabapentin and pregabalin, together with antidepressant drugs, are commonly prescribed to treat SCI-NP, but their efficacy is unsatisfactory. The limited efficacy of current pharmacological treatments for SCI-NP likely reflects our limited knowledge of the underlying mechanism(s) responsible for driving the maintenance of SCI-NP. ⋯ We found that both TTA-P2 and gabapentin reduced mechanical hypersensitivity in male and females SCI rats, but surprisingly only TTA-P2 reduced spontaneous ongoing pain in male SCI rats. PERSPECTIVES: SCI-induced neuropathic pain, and in particular the spontaneous ongoing pain component, is notoriously very difficult to treat. Our data provide evidence that inhibition of T-type calcium channels reduces spontaneous ongoing pain in SCI rats, supporting a clinically relevant role for T-type channels in the maintenance of SCI-induced neuropathic pain.
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Pain catastrophization (PC), involving rumination, magnification, and helplessness, can be viewed as a coping strategy associated with chronic pain. PC is considered a driving force in mediating pain-related outcomes, but it is still unclear whether PC mediates the relationship between psychological and sociodemographic factors with chronic pain when considered in a single model. Using baseline data from a parent study, this study examined the effect of positive and negative psychological and sociodemographic factors on pain severity, interference, and jaw limitation mediated by the PC dimensions in a sample of 397 temporomandibular disorder (TMD) participants using structural equation modeling (SEM). ⋯ Reducing negative cognitions, not just PC, may be of greatest benefit to the most vulnerable TMD populations. PERSPECTIVE: This study examines sociodemographic and psychological factors that affect orofacial pain, finding that the pain catastrophizing dimensions do not mediate these relationships. Understanding which factors most strongly affect pain outcomes will help identify targets for intervention to produce the greatest benefit for the most vulnerable persons suffering from pain.
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Nerve injury outcomes might be predicted by examining small extracellular vesicles (sEVs) in circulation, as their biomolecular cargo facilitates cellular communication and can alter transcriptional state and behavior of recipient cells. We found that sEVs from the serum of spared nerve injury (SNI) model male mice had 7 differentially expressed miRNAs compared to sEVs from sham-operated control mice 4 weeks postsurgery. We investigated how these sEVs alter transcription in primary cortical microglia, a crucial mediator of neuropathic pain, using RNA sequencing. ⋯ Thus, when using sEVs from sham mice as control in comparative mechanistic studies after nerve injury, sex of mice should be taken into consideration. PERSPECTIVE: Microglial uptake of sEVs from male sham control mice induces higher pro-inflammatory responses compared to SNI sEVs but the reverse was observed upon treatment with sEVs from female mice. Wound healing may have a long-term impact on sEVs in male mice and should be considered for comparative studies using sEVs.
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Opioids are powerful analgesics commonly used in pain management. However, opioids can induce complex neuroadaptations, including synaptic plasticity, that ultimately drive severe side effects, such as pain hypersensitivity and strong aversion during prolonged administration or upon drug withdrawal, even following a single, brief administration. The lateral parabrachial nucleus (LPBN) in the brainstem plays a key role in pain and emotional processing; yet, the effects of opioids on synaptic plasticity in this area remain unexplored. ⋯ Thus, we uncovered previously unknown forms of opioid-induced long-term plasticity in the parabrachial nucleus that potentially modulate some adverse effects of opioids. PERSPECTIVE: We found a previously unrecognized site of opioid-induced plasticity in the lateral parabrachial nucleus, a key region for pain and emotional processing. Unraveling opioid-induced adaptations in parabrachial function might facilitate the identification of new therapeutic measures for addressing adverse effects of opioid discontinuation such as hyperalgesia and aversion.
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Affective disruptions, particularly deficits in positive affect, are characteristic of fibromyalgia (FM). The Dynamic Model of Affect provides some explanations of affective disruptions in FM, suggesting that the inverse association between positive and negative emotions is stronger when individuals with FM are under greater stress than usual. However, our understanding of the types of stressors and negative emotions that contribute to these affective dynamics is limited. ⋯ In addition, having a more nuanced understanding of the role that different negative emotions play may be similarly important to understanding emotional dynamics in FM. PERSPECTIVE: This article presents new findings on the emotional dynamics in FM during times of increased pain, fatigue, and stress. Findings highlight the need for clinicians to conduct a comprehensive evaluation of fatigue, stress, and anger in addition to more routinely assessed depression and pain when working with individuals with FM.