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Migraine is a widespread and debilitating neurological condition affecting more than a billion people worldwide. Thus, more effective migraine therapies are highly needed. In the last decade, two endogenous neuropeptides, calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP), were identified to be implicated in migraine. Recently, introduction of monoclonal antibodies (mAbs) blocking the CGRP is the most important advance in migraine therapy for decades. However, 40% of patients are unresponsive to these new drugs. We believe that PACAP may be involved in these patients. Like CGRP, PACAP is located to sensory nerve fibers, it dilates cranial arteries, it causes migraine when infused into patients and it is a peptide that lends itself to antibody therapy. Also, recent studies suggest that the PACAP pathway is independent of the CGRP pathway. Understanding the signaling pathways of PACAP may therefore lead to identification of novel therapeutic targets of particular interest in patients unresponsive to anti-CGRP therapy. Accordingly, neutralizing mAb to PACAP is currently in clinical phase II development. The aim of the present review is, therefore, to give a thorough account of the existing data on PACAP, its receptors and its relation to migraine.

The development of psychedelics as medicines faces several challenges.

The physical limitations experienced by people with chronic pain (CP) produce a greater need for care and assistance, most of which is provided by an informal caregiver (IC). Despite the key role ICs play in the everyday lives of individuals living with CP, knowledge about their experiences and needs is limited. We aimed to address this limitation by exploring the experiences of IC of people with CP.

Despite accumulating evidence indicating reciprocal interrelations between pain and alcohol consumption, no prior work has examined pain as a proximal antecedent of drinking. The goal of the current study was to test the effects of experimental pain induction on ad-lib alcohol consumption among moderate-to-heavy drinkers without chronic pain ( = 237; 42% female; 37% Black; = 3.26). Participants were randomized to either pain-induction (capsaicin + thermal heat paradigm) or no-pain-control conditions. Experimental pain induction lasted for 15 minutes, during which ad-lib alcohol consumption was assessed using an established taste test paradigm. As hypothesized, results indicated that participants randomized to the pain-induction condition poured and consumed more alcohol and reached a higher peak blood alcohol concentration than those randomized to the no-pain condition (s < 0.05; η² range = 0.018-0.021). Exploratory analyses revealed the effects of pain on alcohol consumption to be most pronounced among participants who self-identified as male or Black (relative to female or White, respectively). These findings indicate that the experience of pain serves as a causal, situational motivator for alcohol consumption, and suggest that current drinkers may be susceptible to escalating their consumption of alcohol in the context of pain. Future research is needed to explicate observed differences in the effects of pain on drinking as a function of gender and race, and to extend this work to individuals with chronic pain and varying levels of alcohol use. Collectively, these findings may help inform the development of integrated treatments to address co-occurring pain and alcohol use. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Interrelations between alcohol use disorder and chronic pain have received increasing empirical attention, and several lines of evidence support the possibility of shared genetic liability. However, research on the genetic contributions to the component processes of these complex and potentially overlapping phenotypes remains scarce. The goal of the present study was to test polygenic risk scores (PRSs) for alcohol consumption and multisite chronic pain as predictors of ad lib drinking behavior during an experimental taste test. PRSs were calculated for 209 pain-free, moderate-to-heavy drinkers (57.9% male; 63.6% White). Among White participants, the alcohol and chronic pain PRSs showed nominally significant (s < .05) positive associations with the volume of alcohol consumed and peak blood alcohol concentration (BAC), respectively. However, associations did not survive correction for multiple comparisons. When stratifying results by experimental condition (between-subjects design: no-pain vs. pain), the alcohol PRS was significantly and negatively associated with the volume of alcohol poured, consumed, and peak BAC among Black participants randomized to the no-pain condition (all false discovery rate [FDR] < .05). Conversely, the chronic pain PRS was significantly and positively associated with study outcomes among White participants in both the no-pain (alcohol consumed; FDR = .037) and pain conditions (peak BAC; FDR = .017). These findings lend partial support to the assertion that alcohol consumption in the laboratory is reflective of drinking behavior in naturalistic settings. This was also the first study to use a pain-related PRS to predict alcohol outcomes, which may be indicative of shared etiology between base and target traits. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Innate immune cells play important roles in tissue injury and repair following acute myocardial infarction (MI). Although reprogramming of macrophage metabolism has been observed during inflammation and resolution phases, the mechanistic link to macrophage phenotype is not fully understood. In this study, we found myeloid specific deletion of mitochondrial Complex I protein Ndufs4 (mKO) reproduced the proinflammatory metabolic profile in macrophages and exaggerated the response to lipopolysacharride. Moreover, mKO mice showed increased mortality, poor scar formation and worsened cardiac function 30 days post-MI. We observed a greater inflammatory response in mKO on day 1 followed by increased cell death of infiltrating macrophages and blunted transition to reparative phase during day 3-7 post-MI. Efferocytosis is markedly impaired in mKO macrophages leading to lower expression of anti-inflammatory cytokine and tissue repair factors, which suppressed the proliferation/activation of myofibroblasts in the infarct area. Mitochondria-targeted ROS scavenging rescued these impairments and improved myofibroblast function in vivo and reduced post-MI mortality in mKO mice. Together these results reveal a novel role of mitochondria in inflammation resolution and tissue repair via modulating efferocytosis and crosstalk with fibroblasts. The findings are significant for post-MI recovery as well as for other inflammatory conditions.

While a causal relationship between pain-related fear and spinal movement avoidance in patients with chronic low back pain (CLBP) has frequently been postulated, evidence supporting this relationship is limited. This study aimed to test if decreases in pain-related fear or catastrophizing were associated with improvements in spinal biomechanics, accounting for possible changes in movement-evoked pain.