Left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation reduces the development of long-term muscle pain

The left dorsolateral prefrontal cortex (DLPFC) is involved in the experience and modulation of pain, and may be an important node linking pain and cognition. Repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC can reduce chronic and experimental pain. However, whether left DLPFC rTMS can influence the development of chronic pain is unknown. Using repeated intramuscular injection of nerve growth factor to induce the development of sustained muscle pain (lasting weeks), 30 healthy individuals were randomized to receive 5 consecutive daily treatments of active or sham left DLPFC rTMS, starting before the first nerve growth factor injection on day 0. Muscle soreness and pain severity were collected daily for 14 days and disability on every alternate day. Before the first and 1 day after the last rTMS session, anxiety, depression, affect, pain catastrophizing, and cognitive performance on the attention network test were assessed. Left DLPFC rTMS treatment compared with sham was associated with reduced muscle soreness, pain intensity, and painful area (P < 0.05), and a similar trend was observed for disability. These effects were most evident during the days rTMS was applied lasting up to 3 days after intervention. Depression, anxiety, pain catastrophizing, and affect were unchanged. There was a trend toward improved cognitive function with rTMS compared with sham (P = 0.057). These data indicate that repeated left DLPFC rTMS reduces the pain severity in a model of prolonged muscle pain. The findings may have implications for the development of sustained pain in clinical populations

Individual differences in pain sensitivity are associated with cognitive network functional connectivity following one night of experimental sleep disruption.

Previous work suggests that sleep disruption can contribute to poor pain modulation. Here, we used experimental sleep disruption to examine the relationship between sleep disruption-induced pain sensitivity and functional connectivity (FC) of cognitive networks contributing to pain modulation. Nineteen healthy individuals underwent two counterbalanced experimental sleep conditions for one night each: uninterrupted sleep versus sleep disruption. Following each condition, participants completed functional MRI including a simple motor task and a noxious thermal stimulation task. Pain ratings and stimulus temperatures from the latter task were combined to calculate a pain sensitivity change score following sleep disruption. This change score was used as a predictor of simple motor task FC changes using bilateral executive control networks (RECN, LECN) and the default mode network (DMN) masks as seed regions of interest (ROIs). Increased pain sensitivity after sleep disruption was positively associated with increased RECN FC to ROIs within the DMN and LECN (F(4,14) = 25.28, pFDR = 0.05). However, this pain sensitivity change score did not predict FC changes using LECN and DMN masks as seeds (pFDR &gt; 0.05). Given that only RECN FC was associated with sleep loss-induced hyperalgesia, findings suggest that cognitive networks only partially contribute to the sleep-pain dyad

High frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex modulates sensorimotor cortex function in the transition to sustained muscle pain

Based on reciprocal connections between the dorsolateral prefrontal cortex (DLPFC) and basal-ganglia regions associated with sensorimotor cortical excitability, it was hypothesized that repetitive transcranial magnetic stimulation (rTMS) of the left DLPFC would modulate sensorimotor cortical excitability induced by muscle pain. Muscle pain was provoked by injections of nerve growth factor (end of Day-0 and Day-2) into the right extensor carpi radialis brevis (ECRB) muscle in two groups of 15 healthy participants receiving 5 daily sessions (Day-0 to Day-4) of active or sham rTMS. Muscle pain scores and pressure pain thresholds (PPTs) were collected (Day-0, Day-3, Day-5). Assessment of motor cortical excitability using TMS (mapping cortical ECRB muscle representation) and somatosensory evoked potentials (SEPs) from electrical stimulation of the right radial nerve were recorded at Day-0 and Day-5. At Day-0 versus Day-5, the sham compared to active group showed: Higher muscle pain scores and reduced PPTs (P < 0.04); decreased frontal N30 SEP (P < 0.01); increased TMS map volume (P < 0.03). These results indicate that muscle pain exerts modulatory effects on the sensorimotor cortical excitability and left DLPFC rTMS has analgesic effects and modulates pain-induced sensorimotor cortical adaptations. These findings suggest an important role of prefrontal to basal-ganglia function in sensorimotor cortical excitability and pain processing

Brain changes associated with cognitive and emotional factors in chronic pain : a systematic review

An emerging technique in chronic pain research is MRI, which has led to the understanding that chronic pain patients display brain structure and function alterations. Many of these altered brain regions and networks are not just involved in pain processing, but also in other sensory and particularly cognitive tasks. Therefore, the next step is to investigate the relation between brain alterations and pain related cognitive and emotional factors. This review aims at providing an overview of the existing literature on this subject. Pubmed, Web of Science and Embase were searched for original research reports. Twenty eight eligible papers were included, with information on the association of brain alterations with pain catastrophizing, fear-avoidance, anxiety and depressive symptoms. Methodological quality of eligible papers was checked by two independent researchers. Evidence on the direction of these associations is inconclusive. Pain catastrophizing is related to brain areas involved in pain processing, attention to pain, emotion and motor activity, and to reduced top-down pain inhibition. In contrast to pain catastrophizing, evidence on anxiety and depressive symptoms shows no clear association with brain characteristics. However, all included cognitive or emotional factors showed significant associations with resting state fMRI data, providing that even at rest the brain reserves a certain activity for these pain-related factors. Brain changes associated with illness perceptions, pain attention, attitudes and beliefs seem to receive less attention in literature. Significance: This review shows that maladaptive cognitive and emotional factors are associated with several brain regions involved in chronic pain. Targeting these factors in these patients might normalize specific brain alterations

Heritability of pain catastrophizing and associations with experimental pain outcomes: a twin study

This study used a twin paradigm to examine genetic and environmental contributions to pain catastrophizing and the observed association between pain Catastrophizing and cold-pressor task (CPT) outcomes. Male and female monozygotic (n = 206) and dizygotic twins (n = 194) torn the University of Washington Twin Registry completed a measure of pain catastrophizing and performed a CPT challenge, As expected, pain catastrophizing emerged as a significant predictor of several CPT outcomeS, including cold-pressor Immersion Tolerance, Pain Tolerance, and Delayed Pain Rating. The heritability estimate for pain catastrophizing was found to be 37% with the remaining 63% of variance attributable to unique environmental influence. Additionally, the Observed associations between pain catastrophizing and CPT outcomes were not found attributable to shared genetics or environmental exposure, which suggests a direct relationship between catastrophizing and experimental pain. outcomes. This Study is the first to examine the heritability of pain catastrophizing and potential processes by which pain catastrophizing is related to experimental pain response

The effects of menstrual-related pain on attentional interference

Pain-related attentional interference has been found in both chronic pain and laboratory-inducted pain settings. However, few studies have examined such interference effects during common everyday painful episodes. Menstrual cycle-related pain is a common pain that affects a large number of women on a regular basis. The purpose of the current study was, therefore, to examine the effects of menstrual pain on attentional interference. Fifty-two healthy adult women were tested during 2 different phases of their menstrual cycles: once during a nonpain phase (mid follicular), and once while experiencing menstrual pain (late luteal/early follicular). On each testing session, participants received a battery of 4 attentional interference tasks that included selective attention (flanker task), attention span (n-back task), attentional switching (switching task), and divided attention (dual task). Greater attentional interference effects were found to occur during the menstrual pain phase compared to the nonpain phase. Interestingly, the nature of this effect was a general worsening in performance (eg, slowing, less accurate), rather than a specific attentional deficit. These results add to a growing literature that generally indicates that attentional interference occurs across a range of different types of pain, including common painful episodes. However, they also highlight that the specific nature of this interference effect may depend on the type pain under consideration. Implications of these findings are also considered. © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved