Effects of cannabinoid type 2 receptor agonist AM1241 on morphine-induced antinociception, acute and chronic tolerance, and dependence in mice

Morphine is a potent opioid analgesic used to alleviate moderate or severe pain. The repeated administration of morphine for long periods of time is, however, limited by its propensity to cause tolerance, which reduces antinociceptive efficacy, and by physical dependence, which leads to withdrawal symptoms on discontinuation of the drug.[25] The clinical effectiveness of morphine in pain management is seriously restricted by the development of tolerance and dependence and new strategies are needed for better treatment of pain.

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Enhancing Placebo Effects in Somatic Symptoms Through Oxytocin

Objective Placebo effects relieve various somatic symptoms, but it is unclear how they can be enhanced to maximize positive treatment outcomes. Oxytocin administration may potentially enhance placebo effects, but few studies have been performed, and they have had conflicting findings. The study aim was to investigate the influence of positive verbal suggestions and oxytocin on treatment expectations and placebo effects for pain and itch. Methods One hundred eight female participants were allocated to one of the following four groups: (1) oxytocin with positive verbal suggestions, (2) placebo with positive verbal suggestions, (3) oxytocin without suggestions, and (4) placebo without suggestions. The administration of 24 IU oxytocin or a placebo spray was preceded by positive verbal suggestions regarding the pain- and itch-relieving properties of the spray or no suggestions, depending on group allocation. Pain was assessed with a cold pressor test, and itch was assessed with histamine iontophoresis. Results Positive verbal suggestions induced expectations of lower pain (F = 4.77, p = .031) and itch (F = 5.38, p = .022). Moreover, positive verbal suggestions elicited placebo analgesia (F = 5.48, p = .021) but did not decrease itch. No effect of oxytocin on the placebo effect or on expectations was found. Conclusions Positive suggestions induced placebo analgesia but oxytocin did not enhance the placebo effect. Study limitations are that we only included a female sample and a failure to induce placebo effect for itch. Future studies should focus on how oxytocin might influence placebo effects, taken into account the role of sex, dose-dependent effects, and various expectation manipulations. Trial registration: The study was registered as a clinical trial on www.trialregister.nl (number 6376).

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To treat pain, study people in all their complexity

To treat pain, study people in all their complexity

To treat pain, study people in all their complexity , Published online: 01 May 2018; doi:10.1038/d41586-018-04994-5

Clinical research needs to investigate not simply drugs, but the psychology of why and how individuals experience pain, says Beth Darnall.

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Associations Between Catecholaminergic and Serotonergic Genes and Persistent Breast Pain Phenotypes Following Breast Cancer Surgery

In the United States, each year more than 230,000 women are diagnosed with breast cancer.66 The majority will undergo breast conserving surgery or mastectomy as part of their treatment regimen. Unfortunately, persistent pain following these procedures is a common problem that has deleterious effects on patients’ functional status and quality of life (QOL).23,43,68 Estimates of persistent pain following breast cancer surgery range from 25% to 60%.23 This type of persistent pain is characterized by burning, throbbing, or aching in the ipsilateral chest, axilla, and/or arm, and is associated with swelling and weakness.

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“I was a little surprised”: Qualitative Insights from Patients Enrolled in a 12-Month Trial Comparing Opioids to Non-Opioid Medications for Chronic Musculoskeletal Pain

Chronic musculoskeletal pain is a major public health problem, associated with disabling physical and emotional consequences for patients and with significant costs related to medical treatment and lost worker productivity.16 Use of opioid analgesics to treat chronic pain has increased dramatically in recent years,7,25 paralleled by increases in opioid-related harms, including addiction and death.1,23,34 While harms of opioids have become apparent, evidence for long-term effectiveness of opioids for chronic pain is lacking; a recent systematic review found no randomized trials that examined effects of opioids on pain, function, or quality of life at one year or longer.

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Oxidative stress contributes to fracture/cast-induced inflammation and pain in a rat model of complex regional pain syndrome

Complex regional pain syndrome (CRPS) develops after a range of injuries including fractures and soft tissue trauma to the extremities.43 The underlying mechanism of CRPS has not been fully elucidated and there are no specific medications approved for the treatment of CRPS. Oxidative stress results from an imbalance between ROS production and antioxidant defense systems. ROS have been implicated in many degenerative neurological conditions, such as Alzheimer's disease1 and Parkinson's disease18 and oxidative stress may also contribute to pain in various diseases, including fibromyalgia,26 diabetes,35,48 and CRPS.

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Psychological factors predict an unfavorable pain trajectory after hysterectomy: a prospective cohort study on chronic postsurgical pain

Chronic postsurgical pain (CPSP) is a well-recognized potential complication with negative personal, social, and health care consequences. However, limited data exist on CPSP and on the course of pain over time after hysterectomy. Using data from a prospective cohort study on a consecutive sample assessed at 4 time points, presurgery (T1), 48 hours (T2), 4 months (T3), and 5 years postsurgery (T4), we sought to examine women's PSP trajectories using assessments of pain at T3 and T4. In addition, this study aimed to investigate presurgical and postsurgical risk factors associated with an unfavourable pain trajectory (PT). Based on pain data collected at T3 and T4, 3 distinct trajectories of PSP emerged: no CPSP (PT1; n = 88), prolonged PSP (PT2; n = 53), and CPSP (PT3; n = 29). Moreover, reported CPSP prevalence at 5 years was 17.1%. Multinomial logistic regression models controlling for age, presurgical pain, and type of hysterectomy tested for baseline and acute postsurgical predictive variables. Membership in PT2 and PT3 was predicted by presurgical anxiety (odds ratio [OR] = 1.131, P = 0.015; OR = 1.175, P = 0.009, respectively), emotional representation of the surgical disease (OR = 1.155, P = 0.034; OR = 1.213, P = 0.020, respectively), and pain catastrophizing (OR = 1.079, P = 0.043; OR = 1.143, P = 0.001, respectively). Furthermore, acute PSP intensity and frequency determined membership of women in PT3 (OR = 1.211, P = 0.033; OR = 3.000, P = 0.029, respectively), and postsurgical anxiety (OR = 1.182, P = 0.026) also played a key predictive role. This study identified factors that can be easily screened before and after surgery and are amenable to change through carefully designed timely and tailored interventions for women at risk of an unfavorable PSP trajectory posthysterectomy.

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