Psychology

Alcohol use disorder (AUD) and chronic pain are complex and debilitating conditions that are difficult to treat, lead to enormous economic costs, and excessive suffering. The difficulty in developing new treatments for AUD is partially due to the lack of consideration given to the wide array of factors that drive alcohol intake. Clinical data suggest that both men and women with chronic pain are more likely to develop alcohol use disorder and report using alcohol to deal with chronic pain. Additionally, it has been shown that self-report of chronic pain correlates with alcohol relapse after a period of abstinence. These data led to the hypothesis that neural mechanisms that contribute to alcohol related behaviors are different in individuals that are also experiencing chronic pain. To test this hypothesis, we used a conditioned place preference (CPP) paradigm to model ethanol seeking in male and female rodents that had undergone either a spared nerve injury (SNI) model of chronic pain or a sham surgery. To determine a dose of ethanol that may be selectively rewarding to injured animals, we first tested the analgesic effects of multiple doses of ethanol on pain-related behaviors in SNI and Sham mice. The higher doses of 1.0g/kg and 2.0g/kg (i.p.) of ethanol were anti-allodynic in SNI mice and analgesic in sham mice. However, we found that the lower dose 0.5 g/kg of ethanol was able to fully reverse mechanical hypersensitivity in SNI animals, while not influencing mechanical thresholds in sham mice. Thus, we conditioned mice using 0.5g/kg of ethanol. We found this dose induced a modest conditioned place preference for the ethanol-paired chamber in both SNI and Sham male mice. Mice then underwent extinction training for 1 week, during which time animals were exposed to the CPP apparatus without receiving any ethanol. To investigate relapse-related behavior, we then tested whether painful stimulation would reinstate ethanol seeking behavior. We found that threshold hindpaw stimulation was able to reinstate ethanol seeking behavior in SNI, but not sham animals. This suggests that animals in chronic pain may associate alcohol with pain relief or that chronic pain animals may be more sensitive to stress induced reinstatement when pain is the stressor. We also tested the effect of drug induced reinstatement and found no differences between SNI and Sham mice, leading us to believe that differences found in pain induced reinstatement were selective to that modality. Ongoing work is aimed at determining the effect of ethanol on weight bearing behavior as well as the effect of chronic pain on ethanol seeking and relapse-related behavior in female mice.

Substance use disorders (SUDs) and overdose deaths have reached unprecedented levels despite considerable efforts to develop pharmacotherapies for their treatment and prevention. Chemoattractant cytokines ('chemokines') are immune system messengers that can alter the therapeutic and abuse-related effects of opioids and stimulants. Therefore, the aims of this study were to evaluate the effectiveness of Maraviroc, a CCR5 antagonist, and AMD3100, a CXCR4 antagonist, to alter 1) the self-administration of fentanyl, an opioid, and cocaine, a stimulant, using a food versus drug choice procedure and 2) the analgesic effects of fentanyl in a radiant heat assay. Adult male Sprague Dawley rats were trained to respond under a fixed ratio (FR) 5 on one lever to receive an infusion of fentanyl (n=8), and on an alternate lever to receive food (grain-based pellet). The choice procedure consisted of 5 sequential 20-min components, each separated by a 2-min intercomponent interval. Food was available across all five components, with increasing unit doses of fentanyl (0.00032-0.01 mg/kg/infusion) available during components 2-5; no drug was available during component 1. Once responding stabilized, rats underwent a series of drug pretreatment tests, including: naloxone (1, 3.2 mg/kg; IP), haloperidol (0.01-0.1 mg/kg; IP), Maraviroc (1-17.8 mg/kg; IP), and AMD3100 (1-17.8 mg/kg; IP). A separate cohort of 8 adult male Sprague Dawley rats was used to evaluate the effects of Maraviroc (10 mg/kg; IP), and AMD3100 (10 mg/kg; IP), on paw withdrawal latencies in a thermal nociception procedure following cumulative doses of fentanyl (0.01-0.1 mg/kg; IP). In rats responding for food or fentanyl, naloxone reduced fentanyl choice while increasing choice of food, whereas haloperidol had little effect on the choice for fentanyl, but decreased responding on both levers at large doses. Maraviroc and AMD3100 had similar effects all rats tested, effectively reallocating behavior away from the drug and towards the food reinforcer. At the largest dose tested, Maraviroc (17.8 mg/kg; IP) disrupted behavior in the early portions of the session, suggestive of a sedative effect in some animals. Maraviroc and AMD3100 did not significantly modify the analgesic effects of fentanyl during tests of thermal nociception. These data suggest that antagonism of CXCR4 and CCR5 may be of use in the ongoing effort to develop medications for the treatment of SUDs.

The rapid development of neuromodulation specifically as it pertains to spinal cord stimulation (SCS) has ushered in an era of new and novel waveforms and programming methodologies. Accompanying this evolution has been a significant investment in clinical trials and outcomes-based research solidifying the foundation of SCS while investing in future indications and therapy expansion. Critically evaluating the existing literature to apply these therapies diligently remains vital to the future of neuromodulation.

Pain-related fear and -avoidance crucially contribute to pain chronification. People with chronic pain may adopt costly avoidance strategies above and beyond what is necessary, aligning with experimental findings of excessive fear generalization to safe movements in these populations. Furthermore, recent evidence suggests that, when avoidance is costly, it can dissociate from fear. Here, we investigated whether concurrently measured pain-related fear and costly avoidance generalization correspond in one task. We also explored whether healthy participants avoid excessively despite associated costs, and if avoidance would decrease as a function of dissimilarity from a pain-associated movement. In a robotic arm-reaching task, participants could avoid a low-cost, pain-associated movement trajectory (T+), by choosing a high-cost non-painful movement trajectory (T-), at opposite ends of a movement plane. Subsequently, in the absence of pain, we introduced three movement trajectories (G1-3) between T+ and T-, and one movement trajectory on the side of T- opposite to T+ (G4), linearly increasing in costs from T+ to G4. Avoidance was operationalized as maximal deviation from T+, and as trajectory choice. Fear learning was measured using self-reported pain-expectancy, pain-related fear, and startle eye-blink EMG. Self-reports generalized, both decreasing with increasing distance from T+. In contrast, all generalization trajectories were chosen equally, suggesting that avoidance-costs and previous pain balanced each other out. No effects emerged in the EMG. These results add to a growing body of literature showing that (pain-related) avoidance, especially when costly, can dissociate from fear, calling for a better understanding of the factors motivating, and mitigating, disabling avoidance.

Interventional management of neuropathic pain (NP) is available to the patients who do not obtain satisfactory pain relief with pharmacotherapy. Evidence supporting this is sparse and fragmented. We attempted to summarize and critically appraise the existing data to identify strategies that yield the greatest benefit, guide clinicians, and identify areas that merit further investigation. A two-round Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 26-item questionnaire made by the authors. Consensus on each statement was defined as either at least 80% endorsement or rejection after the 2nd round. Thirty-five and 29 panelists participated in the 1st and 2nd round, respectively. Consensus was reached in 20 out of 26 statements. There is sufficient basis to treat postherpetic neuralgias and complex regional pain syndromes with progressive levels of invasiveness and failed back surgery syndrome with neuromodulation. Radiculopathies and localized NP can be treated with peripheral blocks, neuromodulation, or pulsed radiofrequency. Non-ablative radiofrequency and non-paresthetic neuromodulation are efficacious and better tolerated than ablative and suprathreshold procedures. A graded approach, from least to most invasive interventions has the potential to improve outcomes in many patients with common refractory NP conditions. Preliminary promising data warrant further research on new indications, and technical advances might enhance the safety and efficacy of current and future therapies.

Movement limitation is a common characteristic of chronic pain such that pain prevents the very movement and activity that is most likely to promote recovery. This is particularly the case for pathological pain states such as complex regional pain syndrome (CRPS). One clinical approach to CRPS that has growing evidence of efficacy involves progressive movement imagery training. Graded Motor Imagery (GMI) targets clinical and neurophysiological effects through a stepwise progression through implicit and explicit movement imagery training, mirror therapy and then functional tasks. Here we review experiences from over 20 years of clinical and research experience with GMI. We situate GMI in terms of its historical underpinnings, the benefits and outstanding challenges of its implementation, its potential application beyond CRPS. We then review the neuropathological targets of GMI and current thought on its effects on neurophysiological biomarkers. Perspective This article provides an overview over experiences made with graded motor imagery training over the last 20 years focussing on the treatment of CRPS. It does both cover the theoretical underpinnings for this treatment approach, biomarkers which indicate potential changes driven by GMI, and experiences for achieving optimal treatment results.

To explore the ways in which stigma is experienced, and what strategies are used to manage stigma among patients using medical cannabis to ease suffering from chronic pain.

Chronic pain conditions entail significant personal and societal burdens and improved outreach of evidence-based pain self-management programs are needed. Digital cognitive-behavioral self-management interventions have shown promise. However, evidence is still scarce and several challenges with such interventions for chronic pain exist. Exploring patients' experiences and engagement with digital interventions may be an essential step towards developing meaningful digital self-management interventions for those living with chronic pain.