The journal of pain : official journal of the American Pain Society
-
Chronic pain is a common health problem in humans. The unique properties and valuable clinical applications of analgesic peptides make them attractive pharmacotherapy options for pain control. Numerous targets for pain modulation processes are currently known, including opioid receptors, transient receptor potential (TRP) channels, voltage-gated ion channels, neuronal nicotinic receptors, and neurotensin receptors. ⋯ In addition, PD-1 signaling in non-neuronal cells could alleviate chronic pain by regulating neuroinflammation. Here, we review the potential and challenges of PD-1 as a candidate target for the development of analgesic peptides. PERSPECTIVE: This review paper aims to review recent advances in research on PD-1 in the domain of pain interference, explore how to obtain more promising PD-1 receptor-targeting analgesic peptides based on PD-L1 and analgesic peptide H-20 for relieving pathological pain, and offer potential optimization strategies for follow-up work of H-20.
-
Systemic lupus erythematosus (SLE) is an unpredictable autoimmune disease where the body's immune system mistakenly attacks healthy tissues in many parts of the body. Chronic pain is one of the most frequently reported symptoms among SLE patients. We previously reported that MRL lupus prone (MRL/lpr) mice develop hypersensitivity to mechanical and heat stimulation. ⋯ These findings suggest that targeting the PAR1 and AMPK signaling pathways in the spinal cord may be a useful approach for treating chronic pain caused by SLE. PERSPECTIVE: Our study provides evidence suggesting activation of PAR1 and suppression of AMPK in the spinal cord induces thermal hyperalgesia and mechanical allodynia in a lupus mouse model. Targeting signaling pathways regulating the PAR1 and AMPK could potentially provide a novel approach to the management of chronic pain caused by SLE.
-
Randomized Controlled Trial
Acute ostracism-related pain sensitization in the context of accumulated lifetime experiences of ostracism.
Ostracism (ie, being ignored/excluded) is a form of social adversity that powerfully impacts health and well-being. While laboratory research indicates that experimentally manipulated experiences of ostracism impact pain, findings have been mixed. Prior investigations have not considered moderating or main effects of individual histories of ostracism, and have been limited in the scope of their pain testing. ⋯ People who are stigmatized may therefore experience enhanced pain burden with repeated and accumulating experiences of ostracism. PERSPECTIVE: Results suggest that in the context of accumulated lifetime experiences of ostracism, single experiences of ostracism evoke central sensitization. In this way, ostracism may function to trigger central sensitization and shape socially- and societally-determined patterns of pain burden and disparity.
-
Pain is a significant symptom experienced frequently by individuals with sickle cell disease (SCD). Pain management includes strategies such as oral rehydration, non-pharmacological therapies (eg, massage, relaxation), and oral analgesics and opioids. Shared decision-making around pain management is emphasized repeatedly in recent guidelines; however, research is sparse regarding factors to be considered in shared decision-making approaches including the perceived risks and benefits of opioids. ⋯ Elements of patient and caregiver decision-making identified in this study may be applied to shared decision-making strategies in the clinical setting and future study. PERSPECTIVE: This study illustrates the factors involved in decision-making around home opioid use for pain management in children and young adults with SCD. These findings can be applied to determining shared decision-making approaches around pain management between providers and patients, in accordance with recent SCD pain management guidelines.
-
Depression and thermal hypersensitivity share pathogenic features and symptomology, but their pathophysiologic interactions have not been fully elucidated. Dopaminergic systems in the ventrolateral periaqueductal gray (vlPAG) and dorsal raphe nucleus have been implicated in these conditions due to their antinociception and antidepression effects, although their specific roles and underlying mechanisms remain obscure. In this study, chronic unpredictable mild stress (CMS) was used to induce depression-like behaviors and thermal hypersensitivity in C57BL/6J (wild-type) or dopamine transporter promoter mice to establish a mouse model of pain and depression comorbidity. ⋯ Moreover, using a chemical genetics approach to activate or inhibit dopaminergic neurons in vlPAG ameliorated or exacerbated depression-like behaviors and thermal hypersensitivity, respectively, in dopamine transporter promoter-Cre CMS mice. Collectively these results demonstrated the specific role of vlPAG and dorsal raphe nucleus dopaminergic systems in the regulation of pain and depression comorbidity in mice. PERSPECTIVE: The current study provides insights into the complex mechanisms underlying thermal hypersensitivity induced by depression, and the findings suggest that pharmacological and chemogenetic modulation of dopaminergic systems in the vlPAG and dorsal raphe nucleus may be a promising therapeutic strategy to simultaneously mitigate pain and depression.