Pain
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Growing evidence from pharmacovigilance data and postmortem toxicology reports highlights the misuse potential of gabapentinoids. This study aimed to investigate the risk of serious adverse outcomes (drug misuse, overdose, major trauma), and their risk factors, in primary care patients who are prescribed gabapentinoids. Using the UK Clinical Practice Research Datalink, a matched cohort study calculated adverse event rates separately for gabapentinoid-exposed and unexposed cohorts. ⋯ The association with overdose was stronger for pregabalin than gabapentin. All adverse outcomes were significantly associated with smoking, history of substance misuse, overdose, or a mental health condition and prescription of opioids, benzodiazepines, antidepressants, and Z-drug hypnotics (eg, gabapentin hazard ratios for association of concurrent opioid use: misuse 1.49 [1.47-1.51]; overdose 1.87 [1.78-1.96]; major trauma 1.28 [1.26-1.30]). Our findings highlight the importance of careful patient selection when prescribing gabapentinoids and the need to educate prescribers about the risks of these drugs, particularly in combination with other central nervous system depressants.
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Adverse childhood experiences (ACEs) affect approximately half of all children worldwide. These experiences have been linked to increased pain sensitivity in adulthood and a higher likelihood of developing severe chronic pain. However, most studies have assessed the effects of ACEs retrospectively, long after they occurred, leaving room for other factors to influence the observed outcomes. ⋯ Children with higher PTSS severity displayed pain hypersensitivity regardless of their traumatic exposure level, whereas in children with lower PTSS severity, greater traumatic exposure correlated with pain hypersensitivity. The results suggest that ACEs among children lead to concurrent pain hypersensitivity and distress and may put them at elevated risk of chronic pain early in life. In addition, our findings emphasize the need for identifying children with various PTSS levels to provide tailored interventions and mitigate the long-term negative effects of ACEs.
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The coherent perceptual experience of one's own body depends on the processing and integration of signals from multiple sensory modalities, including vision, touch, and proprioception. Although nociception provides critical information about damage to the tissues of one's body, little is known about how nociception contributes to own-body perception. A classic experimental approach to investigate the perceptual and neural mechanisms involved in the multisensory experience of one's own body is the rubber hand illusion (RHI). ⋯ The illusion was quantified through direct (questionnaire) and indirect (proprioceptive drift) behavioral measures. We found that a nociceptive rubber hand illusion (N-RHI) could be elicited and that depended on the spatiotemporal congruence of visuonociceptive signals, consistent with basic principles of multisensory integration. Our results suggest that nociceptive information shapes multisensory bodily awareness and contributes to the sense of body ownership.
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Understanding the mechanisms that underpin the transition from acute to chronic pain is critical for the development of more effective and targeted treatments. There is growing interest in the contribution of glial cells to this process, with cross-sectional preclinical studies demonstrating specific changes in these cell types capturing targeted timepoints from the acute phase and the chronic phase. In vivo longitudinal assessment of the development and evolution of these changes in experimental animals and humans has presented a significant challenge. ⋯ These advances now permit tracking of glial changes over time and provide the ability to relate these changes to pain-relevant symptomology, comorbid psychiatric conditions, and treatment outcomes at both a group and an individual level. In this article, we summarize evidence for gliosis in the transition from acute to chronic pain and provide an overview of the specific radiotracers available to measure this process, highlighting their potential, particularly when combined with ex vivo / in vitro techniques, to understand the pathophysiology of chronic neuropathic pain. These complementary investigations can be used to bridge the existing gap in the field concerning the contribution of gliosis to neuropathic pain and identify potential targets for interventions.
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Nociplastic pain, characterized by abnormal pain processing without an identifiable organic cause, affects a significant portion of the global population. Unfortunately, current pharmacological treatments for this condition often prove ineffective, prompting the need to explore new potential targets for inducing analgesic effects in patients with nociplastic pain. In this context, toll-like receptors (TLRs), known for their role in the immune response to infections, represent promising opportunities for pharmacological intervention because they play a relevant role in both the development and maintenance of pain. ⋯ In addition, we explore the association between nociplastic pain and psychiatric comorbidities, proposing that modulating TLRs can potentially alleviate both pain syndromes and related psychiatric disorders. Finally, we discuss the potential sex differences in TLR signaling, considering the higher prevalence of nociplastic pain among women. Altogether, this review aims to shed light on nociplastic pain, its underlying mechanisms, and its intriguing relationship with TLR signaling pathways, ultimately framing the potential therapeutic role of TLRs in addressing this challenging condition.