Individuals engaging in self-injurious behavior (SIB) frequently report absence of pain during acts of SIB. While altered pain sensitivity is discussed as a risk factor for the engagement in SIB, results have been mixed with considerable variance across reported effect sizes, in particular with respect to the effect of co-morbid psychopathology. The present meta-analysis aimed to summarize the current evidence on pain sensitivity in individuals engaging in SIB and to identify covariates of altered pain processing. Three databases were searched without restrictions. Additionally a hand search was performed and reference lists of included studies were checked for potential studies eligible for inclusion. Thirty-two studies were identified after screening 720 abstracts by two independent reviewers. Studies were included if they reported (i) an empirical investigation, in (ii) humans, including a sample of individuals engaging in (iii) SIB and a group of (iv) healthy controls, (v) receiving painful stimulation. Random-effects meta-analysis was performed on three pain-related outcomes (pain threshold, pain tolerance, pain intensity) and several population- and study-level covariates (i.e. age, sex, clinical etiology) were subjected to meta-regression. Meta-analysis revealed significant main effects associated with medium to large effect sizes for all included outcomes. Individuals engaging in SIB show greater pain threshold and tolerance and report less pain intensity compared to healthy controls. Clinical etiology and age are significant covariates of pain sensitivity in individuals engaging in SIB, such that pain threshold is further increased in borderline personality disorder compared to non-suicidal self-injury. Mechanisms underlying altered pain sensitivity are discussed.

Opioids are the cornerstone medication for the treatment of moderate to severe pain. However, analgesic opioid requirements and the propensity to suffer from aversive opioid effects, including fatal respiratory depression and addiction, vary widely among patients. The factors underlying the substantial response variance remain largely unknown and need clarification for using opioids more effectively in appropriately selected patients. This ongoing study takes advantage of the twin paradigm to estimate the genetic and environmental contributions to inter-individual differences in opioid responses. Evidence of significant heritability will justify more detailed and extensive genomic studies. The enrollment target is 80 monozygotic and 45 dizygotic twin pairs who undergo a target-controlled infusion of the opioid alfentanil and saline placebo in sequential but randomized order. In a laboratory-type setting, well-defined pharmacodynamic endpoints are measured to quantify pain sensitivity, analgesic opioid effects, and aversive opioid effects including respiratory depression, sedation and reinforcing affective responses. First results obtained in 159 participants provide evidence for the feasibility and utility of this interventional study paradigm to estimate familial aggregation and heritability components of relevant drug effects. Areas highlighted in this report include recruitment strategies, required infrastructure and personnel, selection of relevant outcome measures, drug infusion algorithm minimizing pharmacokinetic variability, and considerations for optimizing data quality and quantity without hampering feasibility. Applying the twin paradigm to complex and potentially harmful studies comprehensively characterizing pharmacological response profiles is without much precedent. Methods and first results including heritability estimates for heat and cold pain sensitivity should be of interest to investigators considering similar studies.

Reduced pain perception has been observed in hypertensive individuals and normotensive individuals at risk for high blood pressure and may involve increased endogenous opioid release or receptor sensitivity. The present study examined the issue by administering two subjectively similar but physiologically different forms of the pain-reducing procedure transcutaneous electrical nerve stimulation (TENS). Men varying in resting blood pressure and parental history of hypertension participated in three testing sessions during which was presented (a) high-frequency (100 Hz) TENS; (b) low-frequency (2 Hz) TENS, the type believed to elicit endogenous opioid activity; or (c) no-TENS stimulation. Measurements of blood pressure (BP) and other physiological variables were obtained during this period. Afterwards, two pain stimuli were presented: a series of electric shocks and 5 min of arm ischemia. There was a significant negative association between pain and resting systolic blood pressure (SBP), and pain and parental history of hypertension in the no-TENS and high-frequency TENS conditions that was significantly strengthened by administration of low-frequency TENS. As well, low-frequency TENS produced a modest but significant acute reduction in SBP, especially among those with higher resting levels. These results provide further evidence that opioid mechanisms are involved in blood pressure-related hypoalgesia and blood pressure regulation.