The role of pain modulation in non-suicidal self-injury

Individuals with non-suicidal self-injury (NSSI) behavior tend to report feeling little or no pain when they self-injure. Moreover, in laboratory studies the NSSI population tends to demonstrate reduced sensitivity to painful stimuli. There is reason to believe that hypoalgesia could be a risk factor for developing and maintaining NSSI. Many theories have been proposed to explain the reduced sensitivity to pain in the NSSI population; some examples are dissociation, self-critical cognitive style, and low levels of endogenous opioids. However, the evidence supporting these theories are sparse. To understand why the NSSI population experiences less pain, there is a need for a better understanding of how individuals with NSSI process pain. We wanted to use methods that have been developed to study pain modulation in individuals with long-term pain to characterize the pain modulation system of women with ongoing NSSI. Our general hypothesis was that women with NSSI have a hyper-effective pain modulation system that inhibits pain to a greater extent and facilitates pain to a lesser extent, compared to women without NSSI. In Study I, a non-clinical population (N = 62) was recruited to test a pain testing protocol in order to produce offset analgesia (OA) and onset hyperalgesia (OH). Small deviations in a painful thermal stimulation have been found to produce disproportional hypoalgesic (OA) and hyperalgesic (OH) responses. Different stimulus ranges (±1°C and ±2°C) were included in the protocol to study the dynamic relation between heat and pain. The study was composed of two identical experiments. In experiment 1, we produced OA and OH responses, using ±2°C but not ±1°C. In experiment 2, we only produced OA responses, but no OH responses. Study II investigated if it was possible to induce sensory attenuation of pain in a non-clinical population (N = 40) by comparing self-administered pressure pain threshold to experimenteradministrated pressure pain threshold, using an algometer. An experimental condition, where the participants imagined that they pressed the algometer, was also included in the study, to examine if sensory attenuation could be induced with the help of imagery. Self-administered pressure was found to be less painful, compared to experimenter-administered pressure. Moreover, imagined self-administered pressure was also experienced as less painful than experimenter-administered pressure. Self-induced sensory attenuation of pain could be a factor in explaining hypoalgesia during NSSI. Study III consisted of an extensive battery of pain tests in order to study pain modulation in a sample of women with NSSI (N = 41) and an age-matched control group, consisting of healthy women (N = 40). The study also included a simple pain test combined with fMRI. We found that the NSSI group demonstrated higher pressure and heat pain thresholds, compared to the control group. The NSSI group also demonstrated a larger conditioned pain modulation (CPM) effect, compared to the control group. CPM is a test based on the principle pain inhibits pain, and is a measure of central down-regulation of pain. We found no difference between the groups regarding temporal summation of pain, a measure of pain facilitation, or in heat pain tolerance. Tonic painful heat stimulation produced a larger hemodynamic response in primary and secondary somatosensory cortex in the NSSI group, compared to the control group. In Study IV, we used the combined OA/OH protocol that was evaluated in Study I to study pain modulation in women with NSSI (N = 37) and controls (N = 39). The OA/OH protocol was combined with fMRI. Across groups, both the OA and the OH responses were significant. We also found a difference between the groups regarding the OH response, as the NSSI group demonstrated a weaker OH response, compared to the control group. The OH response was associated with a hemodynamic response in the primary somatosensory cortex, across groups, which suggests that the nociceptive signal was upregulated before reaching the brain. In line with our main hypothesis, we found that the NSSI group inhibited pain to a greater extent (CPM in Study III) and facilitated pain to a lesser extent (OH in Study IV), compared to the control group. These results suggest that women with NSSI have a hyper-effective pain modulation system. There were also results that did not support our main hypothesis; the NSSI group did not demonstrate weaker pain facilitation when tested with the temporal summation protocol (Study III) or stronger inhibition associated with OA (Study IV). An explanation could be that different pain tests measure different aspects of pain modulation and only certain pain modulation mechanisms are affected in the NSSI population. The studies of this thesis provide evidence that the previous findings of hypoalgesia in the NSSI population does not reflect response bias but is rooted in how the nervous system modulates nociceptive signals

Förstapersonsbeskrivningar och förstapersonsmetoder i Francisco Varelas neurofenomenologiska forskningsprogram

The present paper critically examines the epistemic status of first-person accounts and first-person methods in Francisco Varela’s research program neurophenomenology, which integrates a phenomenological perspective in cognitive science. The paper also questions Varela’s description of neurophenomenology as an ontological recategorization of nature and a solution to the hard problem of consciousness

Rubber hand illusion and experiences of dissociation in women with self-injury behavior

Background: Illusory ownership over a rubber limb, as observed in the experimental paradigm the rubber hand illusion (RHI), has been reported to be correlated with self-reported dissociative symptoms in patients with current and remitted borderline personality disorder. The aim of the present study was to assess the association between RHI and dissociative symptoms in women with non-suicidal self-injury (NSSI), a patient group reporting high levels of dissociative symptoms. Methods: 41 women with NSSI and a healthy control group of 40 women were included in the study. The RHI was induced by administering tactile stimulation with a soft brush to the participants’ hand and a rubber hand. One congruent condition (synchronous brushing) and one incongruent condition (asynchronous brushing) was compared. The strength of the illusion was measured with the RHI questionnaire and proprioceptive drift. Trait dissociation was measured with the Dissociative Experience Scale-II. Results: Both the NSSI group (p < .001) and control group (p < .001) reported illusory ownership during the experiment, but there was no statistically significant difference in illusory ownership (p = .694) or proprioceptive drift (p = .219) between NSSI and controls. Illusory ownership did not correlate with trait dissociation symptoms in the NSSI group. Discussion: The RHI was induced in both groups but was not more pronounced in NSSI and did not correlate with dissociative symptoms. The results are consistent with some of the previous efforts to establish a relationship between illusory ownership and borderline personality disorder

Placebo response and media attention in randomized clinical trials assessing cannabis-based therapies for pain: a systematic review and meta-analysis.

IMPORTANCE Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements. OBJECTIVE To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention. DATA SOURCES A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered. STUDY SELECTION Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders. DATA EXTRACTION AND SYNTHESIS The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model. MAIN OUTCOMES AND MEASURES Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g). RESULTS Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q1 = 5.47; I2 = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes. CONCLUSIONS AND RELEVANCE Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief

Augmented pain inhibition and higher integration of pain modulatory brain networks in women with self-injury behavior

Individuals who engage in nonsuicidal self-injury (NSSI) have demonstrated insensitivity to pain compared with individuals without NSSI. Yet, the neural mechanisms behind this difference are unknown. The objective of the present study was to determine which aspects of the pain regulatory system that account for this decreased sensitivity to pain. In a case-control design, 81 women, aged 18-35 (mean [SD] age, 23.4 [3.9]), were included (41 with NSSI and 40 healthy controls). A quantitative sensory testing protocol, including heat pain thresholds, heat pain tolerance, pressure pain thresholds, conditioned pain modulation (assessing central down-regulation of pain), and temporal summation (assessing facilitation of pain signals) was used. Pain-evoked brain responses were assessed by means of fMRI scanning during thermal pain. NSSI participants showed a more effective central down-regulation of pain, compared to controls, assessed with conditioned pain modulation. The neural responses to painful stimulation revealed a stronger relation between nociceptive and pain modulatory brain regions in NSSI compared to controls. In line with previous studies, pressure and heat pain thresholds were higher in participants with NSSI, however, there were no correlations between pain outcomes and NSSI clinical characteristics. The augmented pain inhibition and higher involvement of pain modulatory brain networks in NSSI may represent a pain insensitive endophenotype associated with a greater risk for developing self-injurious behavior