[Assessing pain in patients with dementia]. / Schmerzerfassung bei Patienten mit Demenz.

The diagnostics of pain in older people with cognitive impairments should always consist of a subjective self-report of pain and a structured observation of pain behavior. It is important to note that the subjective self-report of pain becomes less valid with increasing cognitive decline (starting with a moderate degree of dementia). The external observation of pain behavior should include at least the three behavioral domains facial expressions, body movements and vocalization and should be performed during resting situations and during activities of daily living. Moreover, the patient should be observed for at least 3 min. Online forms of training have recently been developed and are freely available for training in external observation.

Psychometric Properties of the German Version of the Pain Vigilance and Awareness Questionnaire (PVAQ) in Pain-Free Samples and Samples with Acute and Chronic Pain.

PURPOSE: The way individuals attend to pain is known to have a considerable impact on the experience and chronification of pain. One method to assess the habitual "attention to pain" is the Pain Vigilance and Awareness Questionnaire (PVAQ). With the present study, we aimed to test the psychometric properties of the German version of the PVAQ across pain-free samples and across patients with acute and chronic pain. METHOD: Two samples of pain-free individuals (student sample (N = 255)/non-student sample (N = 362)) and two clinical pain samples (acute pain patients (N = 105)/chronic pain patients (N = 36)) were included in this cross-sectional evaluation of the German PVAQ. Factor structure was assessed using exploratory and confirmatory factor analyses. Reliability was assessed using internal consistency (Cronbach's alpha). Construct validity was tested by assessing correlations between PVAQ and theoretically related constructs. RESULTS: Exploratory factor analysis (non-student sample) and confirmatory factor analysis (student sample, acute pain patient sample) suggested that a two-factor solution best fitted our data ("attention to pain," "attention to changes in pain"). Internal consistency ranged from acceptable to good in all four samples. As hypothesized, the PVAQ correlated significantly with theoretically related constructs in all four samples, suggesting good construct validity in pain-free individuals and in pain patients. CONCLUSION: The German PVAQ shows good psychometric properties across samples of pain-free individuals and patients suffering from pain that are comparable to PVAQ versions of other languages. Thus, the German PVAQ seems to be a measure of pain vigilance equally valid as found in other countries.

[Sleep deprivation and pain: a review of the newest literature]. / Schlafentzug und Schmerz : Ein Review der neuesten Literatur.

It has now been established that sleep deprivation or fragmentation causes hyperalgesia which cannot be explained by a general change in somatosensory perception. However, it has not yet been clarified which of the sleep stages are most relevant for this effect. The seemingly paradoxical effects of sleep deprivation on pain-evoked brain potentials on the one hand and the subjective pain report on the other hand suggest complex changes in gating mechanisms. As the effects on pain and affect can be dissociated a common mechanism of action seems unlikely. Data from animal studies suggest that hyperalgesia due to sleep deprivation might be particularly strong under preexisting neuropathic conditions. Together with results from animal research the finding that endogenous pain modulation (CPM) is impaired by sleep deprivation suggests that the serotoninergic system mediates the effect of sleep deprivation on pain perception. However, other neurotransmitters and neuromodulators still have to be considered. The clinically relevant question arises why sleep deprivation induces hyperalgesia more easily in certain individuals than in others and why this effect then has a longer duration?

[Psychological prophylaxis training for coping with postoperative pain. Long-term effects]. / Psychologisches Prophylaxetraining zur Bewältigung postoperativer Schmerzen. Langfristige Effekte.

INTRODUCTION: The present study was performed to investigate the effect of multidimensional psychological prophylaxis training focusing on coping with cognitive-emotional pain on recovery within the first 12 months after surgery. The training included the following three components: (1) education about pain, analgesia and psychological aspects of coping with pain, (2) training for coping with pain and (3) body-centered relaxation. MATERIAL AND METHODS: In the study 48 young male patients (surgical correction of a chest malformation) were assessed 1 day before surgery, at discharge and 3, 6 and 12 months postoperatively concerning postoperative pain intensity and pain disability as well as pain anxiety, pain catastrophizing and pain hypervigilance. Additionally, 24 of these patients received training on cognitive-emotional coping with pain 1 day before surgery and 1-3 days after surgery (each session 1 h). RESULTS: The proportion of patients with clinically relevant improvement was significantly higher in the training group compared to the control group. This was the case for acute pain intensity (approximately 1 week after surgery), pain disability 3 months later and pain anxiety 12 months after surgery. CONCLUSION: The resurgence of pain anxiety after 12 months could only be found in the control group and could be due to the upcoming surgical removal of the transsternal metal implant. The prophylaxis training can therefore be seen as a protective factor for long-term management of surgery-related consequences and future pain experiences.

[Central pain processing and Parkinson's disease. Epidemiology, physiology, and experimental results issuing pain processing]. / Zentrale Schmerzverarbeitung bei Morbus Parkinson. Epidemiologie, Physiologie und experimentelle Befunde zur Schmerzverarbeitung.

Parkinson's disease (PD) is caused by degeneration of the dopaminergic neurons in the substantia nigra (SN) and a resulting dysfunction of the nigrostriatal pathways including the basal ganglia. Beside motor symptoms, different types of pain (e.g., dystonic musculoskeletal pain or central pain) occur in a considerable number of patients. In addition, abnormalities in pain processing have been observed in PD patients, which may present as increased pain sensitivity. The pathophysiological mechanisms involved in disturbed pain processing of PD, however, are still poorly understood. The present article gives an overview of the relevant experimental studies, investigating the abnormalities of pain processing in PD by means of electrophysiological [electroencephalography (EEG), sympathetic skin response (SSR)] and psychophysical methods [quantitative sensory testing (QST), RIII reflex threshold]. Based on a review of the literature, it is postulated that dysfunction in endogenous pain inhibition caused by dopaminergic deficiency in the basal ganglia, especially in the striatum, but also in mesolimbic areas is a main pathophysiological mechanism involved in nociceptive abnormalities in PD.

Menstrual variation in experimental pain: correlation with gonadal hormones.

BACKGROUND: The results of studies examining the response to experimental pain during the menstrual cycle are conflicting because of differences in the definitions of the menstrual period, outcome measures and types of experimental pain stimulation. So far, there have been only a few studies correlating experimental pain with the levels of gonadal hormones over the menstrual cycle. Therefore, we assessed the responses to multiple experimental pain stimuli during the menstrual cycle and computed their correlations with the salivary concentrations of the gonadal hormones estrogen and testosterone. METHODS: Twenty-four healthy and regularly menstruating women between 20 and 41 years old took part in the study. Detection thresholds (warmth, cold and electrical current) and pain thresholds (cold, heat, pressure and electrical current) were assessed on days 1, 4, 14 and 22 of the menstrual cycle. In each session, salivary samples were collected for the determination of the physiological estrogen 17beta-estradiol, progesterone and testosterone. Progesterone was used exclusively to verify regular menstrual cycling. RESULTS: Significant variations in pain thresholds for cold, pressure and electrical stimuli were observed over the menstrual cycle with the highest thresholds on day 22, except for the cold pain thresholds, which peaked on day 14. There were no such changes regarding heat pain and all the detection thresholds. The correlations separately computed for each of the 4 days between salivary estrogen as well as testosterone on the one hand and the detection or pain thresholds on the other hand failed to show significant levels, except for the coupling of testosterone and electrical pain thresholds on day 1. CONCLUSIONS: The pain thresholds for all the physical stressors increased after menstruation. The acrophases were located in the follicular (cold pain threshold) or in the luteal phase (pressure and electrical pain thresholds). The results of our correlation analyses indicate only minimal influences of the physiological levels of gonadal hormones on pain sensitivity in women.

Pain sensitivity and descending inhibition of pain in Parkinson's disease.

BACKGROUND: Patients suffering from Parkinson's disease (PD) often complain about painful sensations. Recent studies detected increased subjective pain sensitivity and increased spinal nociception, which appeared to be reversible by dopaminergic treatment. Possibly, reduced descending pain inhibition contributes to this finding. OBJECTIVE: Subjective pain thresholds as well as nociceptive reflex thresholds were investigated to isolate potential loci of the pathophysiological changes within the pain pathway. In addition, the diffuse noxious inhibitory control (DNIC) system as one form of descending control was assessed. METHOD: 15 patients with PD and 18 controls participated in the study. Electrical and heat pain thresholds as well as the nociceptive flexion reflex (NFR) thresholds were determined. Thereafter, the electrical pain thresholds were measured once during painful heat stimulation (conditioning stimulation) and twice during innocuous stimulation (control stimulation). RESULTS: Patients with PD exhibited lower electrical and heat pain thresholds as well as lower NFR thresholds. Suppression of the electrical pain thresholds during painful heat stimulation (conditioning stimulation) compared with control stimulation did not differ significantly between the groups. No differences in the thresholds between patients with PD with and without clinical pain were seen. CONCLUSIONS: Finding the NFR threshold to be decreased in addition to the decreased electrical and heat pain thresholds indicates that the pathophysiological changes either already reside at or reach down to the spinal level. Reduced activation of the DNIC system was apparently not associated with increased pain sensitivity, suggesting that DNIC-like mechanisms do not significantly contribute to clinical pain in PD.

Prediction of persistent post-operative pain: Pain-specific psychological variables compared with acute post-operative pain and general psychological variables.

BACKGROUND: Psychological variables and acute post-operative pain are of proven relevance for the prediction of persistent post-operative pain. We aimed at investigating whether pain-specific psychological variables like pain catastrophizing add to the predictive power of acute pain and more general psychological variables like depression. METHODS: In all, 104 young male patients undergoing thoracic surgery for pectus excavatum correction were studied on the pre-operative day (T0) and 1 week (T1) and 3 months (T2) after surgery. They provided self-report ratings (pain-related: Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale = PASS, Pain Vigilance and Awareness Questionnaire = PVAQ; general psychological: Screening for Somatoform Symptoms, State-Anxiety Inventory-X1, Center for Epidemiologic Studies Depression Scale = CES-D). Additional predictors (T1) as well as criterion variables (T2) were pain intensity (Numerical Rating Scale) and pain disability (Pain Disability Index). RESULTS: Three months after surgery, 25% of the patients still reported clinically relevant pain (pain intensity ≥3) and over 50% still reported pain-related disability. Acute post-operative pain as well as general psychological variables did not allow for a significant prediction of persistent post-operative pain; in contrast, pain-related psychological variables did. The best single predictors were PASS for pain intensity and PVAQ for pain disability. CONCLUSIONS: Pain-related psychological variables derived from the fear-avoidance model contributed significantly to the prediction of persistent post-operative pain. The best possible compilation of these measures requires further research. More general psychological variables may become relevant predictors later in the medical history. SIGNIFICANCE: Our results suggest that pain-specific psychological variables such as pain anxiety and pain hypervigilance add significantly to the prediction of persistent post-operative pain and might even outperform established predictors such as acute pain and general psychological variables. Clinicians might benefit from the development of time-economic screening tools based on these variables.

Startle modulation by heat pain with varying threat levels in chronic pain patients and pain-free controls.

BACKGROUND: Empirical evidence suggests that affective responses to pain are changed in chronic pain. The investigation of startle responses to pain might contribute to clarifying whether such alterations also expand to motivational defensive reactions. We aimed at comparing startle responses to tonic heat pain with high threat (HT) or low threat (LT) in patients with chronic musculoskeletal pain and controls. As pain-related anxiety and catastrophizing are typically elevated in chronic pain, we expected to find stronger startle responses in patients specifically under experimental HT. METHODS: Patients with chronic musculoskeletal, preferentially, back pain (N = 19) and matched pain-free controls (N = 19) underwent two pain-related threat conditions (high and low) in balanced order. Only, in the HT condition, 50% of the trials were announced to include a short further noxious temperature increase at the end. Startle responses to loud tones were always assessed prior to a potential temperature increase in the phase of anticipation and were recorded by surface electromyogram. RESULTS: Surprisingly, we observed no differences in startle responses and ratings of emotional and pain responses between patients and controls despite significantly higher pain-related anxiety and catastrophizing in the patients. Overall, startle was potentiated in the HT condition, but only in participants who started with this condition. CONCLUSION: Our results suggest that, in general, patients with pain are not more responsive emotionally to experimental threat manipulations despite elevated pain anxiety and catastrophizing. Instead, exaggerated responses in patients might be triggered only by individual concerns relating to pain, which are not sufficiently mirrored by our threat paradigm.

Improving recognition of pain by calling attention to its various faces.

BACKGROUND: The ability to accurately recognize facial expressions of pain is known to affect clinical decision making and delivery of care. Although recognition accuracy for facial expressions of pain is well above chance level, substantial shortcomings have also been reported which stress the need to look for methods to improve recognition accuracy. Based on findings that pain is encoded in different facial activity patterns, we wanted to investigate whether training observers to recognize these various faces of pain might improve their ability to accurately recognize pain. METHODS: Participants (55 male, 65 female) were randomly assigned to one of the three training groups: 'different patterns group' (calling attention to the various faces of pain); 'prototypical group' (calling attention to the prototypical expression of pain); and 'control group' (being informed about pain in general). For outcome assessments, participants viewed videos of individuals experiencing either pain, disgust or a neutral condition and had to infer what the individual in the video was experiencing. These videos were presented twice (before and after the training). RESULTS: The 'different patterns group' benefited the most from its training, with recognition accuracy for pain increasing significantly more compared to the other groups. The 'prototypical' group also showed improved recognition accuracy for pain, however, this improved recogntition was cancelled out by decreased recognition accuracy for disgust. CONCLUSIONS: Raising awareness in observers that different combinations of facial movements (different faces of pain) are equivalent signals of pain through a brief training procedure can improve recognition accuracy for pain substantially.

Modulation of the startle reflex by heat pain: does threat play a role?

BACKGROUND: Previous studies have indicated that the startle reflex is potentiated by phasic, but not by tonic, heat pain, although the latter is seen as more strongly associated with emotional responses and more similar to clinical pain. The threat value of pain might be a decisive variable, which is not influenced alone by stimulus duration. OBJECTIVE: This study aimed at comparing startle responses to tonic heat pain stimulation with varying degrees of threat. We hypothesized that the expectation of unpredictable temperature increases would evoke higher threat and thereby potentiate startle compared with the expectation of constant stimulation. METHODS: Healthy, pain-free subjects (n = 40) underwent painful stimulation in two conditions (low/high threat) in balanced order. The only difference between the two conditions was that in the high-threat condition 50% of the trials were announced to include a short further noxious temperature increase at the end. Startle tones were presented prior to this temperature increase still in the phase of anticipation. RESULTS: We observed startle potentiation in the high-threat compared with the low-threat condition, but only in those participants who took part first in the high-threat condition. Habituation could not account for these findings, as we detected no significant decline of startle responses in the course of both conditions. CONCLUSIONS: Our results suggest that subjective threat might indeed be decisive for the action of pain on startle; the threat level appears not only influenced by actual expectations but also by previous experiences with pain as threatening or not.

Gaze behaviour when monitoring pain faces: An eye-tracking study.

BACKGROUND: The vigilance-(attentional) avoidance hypothesis (VAH) developed for explaining phobic reactions describes an early attentional bias towards a feared stimulus followed by attentional avoidance of this stimulus. Such a pattern of attentional shifts might also be found when processing of pain-related stimuli is required. The purpose of the present study was to test the VAH for pain-associated stimuli, i.e., faces displaying pain, using the method of eye-tracking in a pain-free sample. METHODS: Forty-eight healthy participants observed pictures of faces displaying pain and other emotions (anger, joy), presented concurrently with neutral faces, while their gaze behaviours were recorded continuously. RESULTS: Analysis of the time course of fixation durations revealed a distinct pattern for pain faces. Participants gazed at pain faces longer than at neutral faces at the beginning (up to 1000 ms) but reduced preference for pain faces increasingly thereafter (up to 2000 ms); this decline in vigilance did not occur for anger and joy faces. Strong fear of pain (Fear of Pain Questionnaire) tended to increase attentional preference for negative faces (pain, anger), a finding, which however did not reach significance. CONCLUSIONS: We assume that initial vigilance for pain-associated stimuli might reflect an adaptive reaction to detect a potentially harmful stimulus. Subsequently, the pain-associated stimulus might be less attended for the purpose of mood regulation when all clear is given in this situation.

No effects of hydrocortisone and dexamethasone on pain sensitivity in healthy individuals.

BACKGROUND: There is some evidence that stress-induced cortisol increase leads to a decrease in pain, while lowering cortisol levels enhances pain sensitivity, but no study has yet investigated both pharmacological enhancement and reduction of cortisol levels in the same individuals. METHODS: Firstly, we tested in 16 healthy individuals whether the treatment with hydrocortisone and dexamethasone, respectively, results in altered pain thresholds. Secondly, we aimed to test whether hormone effects are different across the pain range by using ratings for pain stimuli with varying intensity; and thirdly, we tested whether cortisol levels influence the discrimination ability for painful stimuli. RESULTS: Despite substantial effects of dexamethasone and hydrocortisone administration on cortisol levels, no effect of these drugs was seen in terms of pain sensitivity (pain threshold, pain rating, pain discrimination ability), although comprehensively examined. However, in the placebo condition, a significant negative correlation between cortisol and pain thresholds was seen. Similarly, there were also strong negative associations between cortisol levels in the placebo condition and pain thresholds after drug treatment (especially after hydrocortisone). CONCLUSION: These findings suggest that short-term variations of cortisol do not influence pain sensitivity whereas, in general, high levels of cortisol are associated with increased pain sensitivity, at least for weak to moderate stimuli.

Pain sensitivity in anorexia nervosa and bulimia nervosa.

Pain threshold was measured with short heat stimuli using a contact thermode in 19 patients with anorexia nervosa, 20 patients with bulimia nervosa, and 21 control subjects. Both patient groups had significantly elevated pain thresholds compared with the control subjects. In the total sample, no substantial covariation could be demonstrated among pain threshold and clinical, physiological, metabolic, or psychological data. However, in separate regression analyses pain threshold correlated significantly (negatively) with local skin temperature in the anorectic patients and almost significantly (positively) with body weight in the bulimic patients. This finding suggests that the reduced pain sensitivity in the two kinds of eating disorders might have different causes.

Diurnal variations in pain perception and thermal sensitivity.

Pain and thermal sensitivity thresholds in healthy volunteers were examined for diurnal variations. The subjects were 11 men aged between 22 and 27 years (means = 23.5, S.D. = 1.5). Data were collected for 2 days, with 7 measurements per day. To ensure the pain specificity of the results the subliminal modality, i.e., thermal sensitivity thresholds to warm and cold stimuli, was investigated in addition to the threshold for perception of heat pain. Assessments were made on the right hand and foot, the stimuli being presented with a thermoelectric contact-thermode. Despite the influence of variables other than time of day (45-56% of the total variance), diurnal variations were found for some subjects on the pain threshold measure (significant correlation between days and relatively high frequency of 24 h component in Fourier analysis spectra). However, they could not be demonstrated for the thermal sensitivity measures. The diurnal variations in pain perception thresholds did not have a consistent pattern over all subjects (Friedman test). The small diurnal variations with interindividual differences in the pattern are therefore not sufficient to explain the variations seen in clinical pain, but they may be useful in detecting pain modulators by investigating correlations.

Multi-method assessment of experimental and clinical pain in patients with fibromyalgia.

Experimental measures of responsiveness to painful and non-painful stimuli as well as measures of typical and present clinical pain were assessed in 26 female patients with fibromyalgia and in an equal number of age-matched healthy women. Pressure pain thresholds, determined by means of a dolorimeter, were lower in the patients compared to the control subjects both at a tender point (trapezius) and at a non-tender control point (inner forearm). The same was true for the heat pain thresholds, measured using a contact thermode. In contrast, the pain thresholds for electrocutaneous stimuli were decreased only at the tender point. The detection thresholds for non-painful stimuli (warmth, cold and electrical stimuli) seemed to be less affected in the fibromyalgia patients, with only the detection threshold for cold being lower at both sites. Tender points were more sensitive than control points for mechanical pressure. The reverse was found for the other modalities which were tested. Although the 3 experimental pain thresholds showed patterns of either generalized or site-specific pain hyperresponsiveness, the between-methods correlations were not very high. While the correlations between the experimental pain thresholds and the various measures of clinical pain (Localized Pain Rating, McGill Pain Questionnaire) in the patients were generally low, there were significant negative correlations between pressure pain thresholds at the two sites and the level of present pain assessed by the Localized Pain Rating. We conclude that a pattern of pain hyperresponsiveness, generalized across the site of noxious stimulation and across the physical nature of the stressor, is associated with fibromyalgia.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticotropin-releasing-hormone lacks analgesic properties: an experimental study in humans, using non-inflammatory pain.

The antinociceptive potency of corticotropin-releasing-hormone (CRH) has been established in several animal studies in which both central and peripheral sites of action were considered. However, there have not yet been any experimental trials, besides one attempt using clinical dental pain demonstrating the potential analgesic properties of CRH in humans. For this reason, we studied the effect of CRH on experimental heat pain sensitivity in 18 healthy men, using a double-blind, cross-over and placebo-controlled design. A dose of 100 microg (i.v.) was chosen because of its well-known neuroendocrine effects in humans. The pain parameters assessed were, visual analog scale (VAS) ratings for pain intensity and pain unpleasantness, pain thresholds and scores for discrimination ability. To differentiate between a direct analgesic effect of CRH and indirect effects via evoked hormonal responses in the hypothalamic-pituitary-adrenocortical (HPA) system (beta-endorphin, ACTH, cortisol), CRH was applied with and without a pre-treatment with dexamethasone. In neither of the two conditions was there any systematic change in our pain parameters. This failure to find any evidence suggesting an analgesic action of CRH or of the subsequent hormones of the HPA system was obtained despite the fact that CRH produced clear neuroendocrine responses such as increases in the plasma concentration of beta-endorphin and cortisol. It is unclear whether the lack of analgesic action of CRH is due to its non-existence in humans, due to the use of a pain model which does not assess minute changes in pain sensitivity and does not trigger substantial inflammatory responses, or due to an insufficient dose of CRH.

Pain perception in psychiatric disorders: a review of the literature.

Aberrations of pain experience occur frequently in psychiatric disorders and hence pathological alterations in the basic mechanisms underlying pain experience can be expected. Nevertheless, pain perception, as one of the most important basic mechanisms of pain experience, has rarely been assessed experimentally in psychiatric disorders. The authors review the relevant experimental studies on pain perception in patients with anxiety disorders, schizophrenia, depression, eating disorders and personality disorders and suggest lines for future research. Finally, they point out that the experimental study of pain perception is useful not only in understanding aberrant pain experiences in psychiatric disorders but also in elucidating pathophysiological mechanisms because pain perception is controlled by neurochemical and neurohormonal functions known to be affected by psychiatric disease processes.

Possible deficiencies of pain modulation in fibromyalgia.

OBJECTIVE: To examine possible deficiencies in endogenous pain modulating mechanisms in fibromyalgia patients compared with matched pain-free control subjects. DESIGN/SUBJECTS/METHODOLOGY: Pain reduction was investigated in 25 female patients with fibromyalgia and 26 age-matched healthy women using the diffuse noxious inhibitory controls (DNIC) paradigm. Tonic thermal stimuli at painful and nonpainful intensities, tailored to individual heat pain thresholds, were employed to induce pain inhibition. The anticipated effect was assessed by measuring the electrical pain threshold and detection threshold, using a double staircase method. Only nontender control points were stimulated (thermode on the foot, electrodes on the inner forearm). RESULTS: The patients with fibromyalgia had significantly lower heat pain thresholds than the healthy subjects, but similar electrical detection and pain thresholds. The repeatedly applied electrical stimuli resulted in a degree of perceptual adaptation that was similar between the two groups. However, concurrent tonic thermal stimuli, at both painful and nonpainful levels, significantly increased the electrical pain threshold in the healthy subjects but not in the fibromyalgia patients. The electrical detection threshold was not affected in either group. CONCLUSIONS: Pain modulation, produced by a concurrent tonic stimulus in healthy persons, was not seen in the fibromyalgia group. The patients either had deficient pain modulation or were unable to tolerate a tonic stimulus intense enough to engage a modulatory process. It remains to be established whether the pain reduction found in the healthy subjects was the conventional DNIC effect, another effect (e.g., distraction), or a combination of both.

Sex differences in musculoskeletal pain.

Epidemiologic, clinical, and experimental evidence points to sex differences in musculoskeletal pain. Adult women more often have musculoskeletal problems than do men. Discrepant findings regarding the presence of such differences during childhood and adolescence continue. Biologic and psychosocial factors might account for these differences. The authors review evidence showing that mechanically induced pressure is more likely to show sex differences than other noxious stimuli and to discriminate between individuals suffering from musculoskeletal pain and matched controls. The authors suggest that a state of increased pain sensitivity, with a peripheral or central origin, predisposes individuals to chronic muscle pain conditions, and that there are sex differences in the operation of these mechanisms; women are vulnerable to the development and maintenance of musculoskeletal pain conditions.