Hypoalgesia related to elevated resting blood pressure is absent in adolescents and young adults with a history of functional abdominal pain

Elevated resting blood pressure (BP) is hypoalgesic in healthy individuals, but this effect is absent in adults with chronic somatic pain. This study tested whether BP-related hypoalgesia is similarly altered in individuals with a history of chronic visceral pain in childhood. Resting BP was assessed in 94 adolescents and young adults with a known history of childhood functional abdominal pain (FAP) and 55 comparable healthy controls. Responses to an acute heat pain stimulus were then evaluated following exposure to two laboratory stressors. A significant participant type × systolic BP (SBP) interaction (p < .005) revealed that elevated resting SBP was associated with significantly higher heat pain threshold (p < .001) in healthy controls, but was unrelated to pain threshold in the FAP group. A similar pattern was observed for heat pain tolerance, with elevated SBP linked to significantly higher pain tolerance (p < .05) in healthy controls, but unrelated to tolerance in the FAP group. Dysfunction in BP-related hypoalgesia associated with FAP was evident regardless of whether childhood FAP had resolved or still persisted at the time of laboratory testing. Subgroup analyses indicated that BP-related hypoalgesia (in healthy controls) and FAP-linked absence of this hypoalgesia was observed only among females. Result suggest that childhood visceral chronic pain may be associated with relatively long-lasting dysfunction in overlapping systems modulating pain and BP that persists even after FAP resolves. Potential implications for later hypertension risk are discussed.     

Increased sensitivity to heat pain in chronic low blood pressure

While in elevated blood pressure reduced sensitivity to acute pain has been well established, little is known about possible alterations in pain perception within the lower range of blood pressure. In this study, sensitivity to heat pain was assessed in 40 subjects with chronic hypotension (mean blood pressure 96.5/57.7mmHg) and 40 normotensive control persons (mean blood pressure 121.8/77.2mmHg). Employing a contact thermode, heat stimuli were applied to the forearm. Pain threshold and tolerance were determined. Participants furthermore rated subjective intensities and unpleasantness of tonic heat stimuli (45.5–47.5°C) on visual analogue scales and in a questionnaire. Possible confounding of sensitivity to heat pain with skin temperature, temperature sensitivity and mood was controlled for. In addition to blood pressure, functional features of the arterial baroreceptor system were related to pain experience. Therefore, estimates for the input on the baroreceptors, as well as baroreflex sensitivity were obtained. Hypotensive individuals exhibited markedly reduced pain threshold and pain tolerance, as well as increased sensory and affective pain experience. The measures related to the baroreceptor system were not associated with pain experience, suggesting that no significant modulation of heat pain occurs through this system. The results of this study complete the findings on hypertension‐related hypoalgesia and suggest an inverse relationship between blood pressure and pain sensitivity across the whole blood pressure spectrum. Furthermore, increased proneness of hypotensive individuals to clinical pain may be discussed.     

Adaptability to pain is associated with potency of local pain inhibition,but not conditioned pain modulation: A healthy human study

This study investigated the relationship between pain sensitivity, adaptability, and potency of endogenous pain inhibition, including conditioned pain modulation (CPM) and local pain inhibition. Forty-one healthy volunteers (20 male, 21 female) received conditioning stimulation (CS) over 2 sessions in a random order: tonic heat pain (46°C) on the right leg for 7 minutes and cold pressor pain (1°C to 4°C) on the left hand for 5 minutes. Participants rated the intensity of pain continuously using a 0 to 10 electronic visual analogue scale. The primary outcome measures were pressure pain thresholds (PPT) measured at the heterotopic and homotopic location to the CS sites before, during, and 20 minutes after CS. Two groups of participants, pain adaptive and pain nonadaptive, were identified based on their response to pain in the cold pressor test. Pain-adaptive participants showed a pain reduction between peak pain and pain at end of the test by at least 2 of 10 (n = 16); whereas the pain-nonadaptive participants reported unchanged peak pain during 5-minute CS (n = 25). Heterotopic PPTs during the CS did not differ between the 2 groups. However, increased homotopic PPTs measured 20 minutes after CS correlated with the amount of pain reduction during CS. These results suggest that individual sensitivity and adaptability to pain does not correlate with the potency of CPM. Adaptability to pain is associated with longer-lasting local pain inhibition.     

Persistent post-surgical pain and experimental pain sensitivity in the Tromsø study: Comorbid pain matters

In a large survey incorporating medical examination (N = 12,981), information on chronic pain and surgery was collected, and sensitivity to different pain modalities was tested. Tolerance to the cold pressor test was analysed with survival statistics for 10,486 individuals, perceived cold pressor pain intensity was calculated for 10,367 individuals, heat pain threshold was assessed for 4,054 individuals, and pressure pain sensitivity for 4,689 individuals. Persistent post-surgical pain, defined by self-report, was associated with lower cold pressor tolerance (sex-adjusted hazard ratio = 1.34, 95% confidence interval = 1.08–1.66), but not when adjusting for other chronic pain. Other experimental pain modalities did not differentiate between individuals with or without post-surgical pain. Of the individuals with chronic pain (N = 3352), 6.2% indicated surgery as a cause, although only 0.5% indicated surgery as the only cause. The associations found between persistent post-surgical pain and cold pressor tolerance is largely explained by the co-existence of chronic pain from other causes. We conclude that most cases of persistent post-surgical pain are coexistent with other chronic pain, and that, in an unselected post-surgical population, persistent post-surgical pain is not significantly associated with pain sensitivity when controlling for comorbid pain from other causes. A low prevalence of self-reported persistent pain from surgery attenuates statistically significant associations. We hypothesize that general chronic pain is associated with central changes in pain processing as expressed by reduced tolerance for the cold pressor test.     

Temporal daily associations between pain and sleep in adolescents with chronic pain versus healthy adolescents

Adolescents with chronic pain frequently report sleep disturbances, particularly short sleep duration, night wakings, and poor sleep quality. Prior research has been limited by assessment of subjectively reported sleep only and lack of data on daily relationships between sleep and pain. The current study utilized multilevel modeling to compare daily associations between sleep and pain in adolescents with chronic pain and healthy adolescents. Ninety-seven adolescents (n = 39 chronic pain; n = 58 healthy) aged 12-18, 70.1% female participated. Adolescents completed pain diary ratings (0-10 NRS) and actigraphic sleep monitoring for 10 days. Actigraphic sleep variables (duration, efficiency, WASO) and self-reported sleep quality were tested as predictors of next-day pain, and daytime pain was tested as a predictor of sleep that night. Effects of age, gender, study group, and depressive symptoms on daily associations between sleep and pain were also tested. Multivariate analyses revealed that nighttime sleep (p < .001) and minutes awake after sleep onset (WASO) (p < .05) predicted next-day pain, with longer sleep duration and higher WASO associated with higher pain. Contrary to hypotheses, neither nighttime sleep quality nor sleep efficiency predicted pain the following day. The interaction between nighttime sleep efficiency and study group was significant, with adolescents with pain showing stronger associations between sleep efficiency and next-day pain than healthy participants (p = .05). Contrary to hypotheses, daytime pain did not predict nighttime sleep. Daily associations between pain and sleep suggest that further work is needed to identify specific adolescent sleep behaviors (e.g., compensatory sleep behaviors) that may be targeted in interventions.     

Severe chronic pain is associated with increased 10 year mortality. A cohort record linkage study

Previous research has clearly demonstrated a link between chronic pain and poor health, and has suggested a link with increased mortality, though the latter is less consistent. In 1996 a cohort of 6940 individuals was recruited, and information collected, about reported chronic pain status, general health and socio-demographic details. Ten years later, a record linkage was conducted between these data and the routinely collected national dataset for death registration. Primary cause of death was classified according to ICD-10 codes. Survival analysis was conducted to obtain unadjusted and multi-adjusted hazard ratios (HR) for all-cause, system-specific and disease-specific mortality by chronic pain status. A total of 5858 (84.4%) of individuals from the original cohort were linked, including 1557 (26.6%) who had died. Survival analysis found significant associations between any reported chronic pain and all-cause mortality (HR 1.32, 99% CI, 1.14–1.54) and a number of specific causes. However, when we adjusted for socio-demographic factors and reported long-term limiting illness, the significant association was lost. Survival among those reporting severe chronic pain was significantly worse than among those reporting mild or no chronic pain. After adjustment for socio-demographic factors and reported long-term limiting illness, severe chronic pain remained significantly associated with all-cause mortality (HR 1.49, 99% CI 1.21–1.84) and all circulatory system disease deaths (HR 1.68, 99% CI 1.20–2.35). The evident association between any chronic pain and increased mortality can apparently be explained by confounding caused by socio-demographic factors. However, severe chronic pain is associated with increased risk of mortality, independent of socio-demographic factors.     

A unique association between cognitive inhibition and pain sensitivity in healthy participants

The experience of pain constitutes a complex phenomenon that is determined by and reflects the interplay of many factors, including cognitive functions. Little is known, however, about the precise role of executive functions in pain sensitivity. Importantly, these functions may be directly related to the ability to control pain. The present study evaluated the relationship between pain sensitivity and executive functions in a sample of healthy volunteers. Pain sensitivity was assessed with the cold pressor test. The immersion time, here defined as the time until substantial pain was reported, was measured. Additional pain intensity and pain unpleasantness ratings were obtained as an indication of pain experience. The results revealed a unique association between cognitive inhibition (i.e. the Stroop interference score), but not other executive functions, and immersion time, pain intensity, and pain unpleasantness. Specifically, better cognitive inhibition was related to a reduction in pain sensitivity as evident by an increased immersion time and decreased pain intensity and pain unpleasantness ratings. As such, cognitive inhibition may be an important determinant of pain sensitivity.     

Sex differences in experimental and clinical pain sensitivity for patients with shoulder pain

Previous research demonstrates that men and women differ in the way that they perceive and process pain. Much of this work has been done in healthy adults with a lack of consensus in clinical pain populations. The purpose of this study was to investigate how men and women with shoulder pain differ in their experience of experimental and clinical pain and whether psychological processes differentially affect these responses. Fifty‐nine consecutive subjects (24 women, 35 men) seeking operative treatment for shoulder pain were enrolled in this study. Subjects completed self report questionnaires to assess clinical pain, catastrophizing, anxiety and depression and underwent a series of experimental pain tests consisting of pressure pain, thermal pain (threshold and tolerance), and thermal temporal summation. Results indicated that women experienced greater clinical pain and enhanced sensitivity to pressure pain. Age did not affect the observed sex differences. There were no sex differences in psychological association with experimental and clinical pain in this cohort. The relationship between clinical and experimental pressure pain was stronger in women as compared to men. These findings offer insight into the interactions between biological and psychosocial influences of pain and how these interactions vary by sex.     

The persistence of pain behaviors in patients with chronic back pain is independent of pain and psychological factors

The primary purpose of the present study was to examine the temporal stability of communicative and protective pain behaviors in patients with chronic back pain. The study also examined whether the stability of pain behaviors could be accounted for by patients’ levels of pain severity, catastrophizing, or fear of movement. Patients (n = 70) were filmed on two separate occasions (i.e., baseline, follow-up) while performing a standardized lifting task designed to elicit pain behaviors. Consistent with previous studies, the results provided evidence for the stability of pain behaviors in patients with chronic pain. The analyses indicated that communicative and protective pain behavior scores did not change significantly from baseline to follow-up. In addition, significant test-retest correlations were found between baseline and follow-up pain behavior scores. The results of hierarchical multiple regression analyses further showed that pain behaviors remained stable over time even when accounting for patients’ levels of pain severity. Regression analyses also showed that pain behaviors remained stable when accounting for patients’ levels of catastrophizing and fear of movement. Discussion addresses the potential contribution of central neural mechanisms and social environmental reinforcement contingencies to the stability of pain behaviors. The discussion also addresses how treatment interventions specifically aimed at targeting pain behaviors might help to augment the overall impact of pain and disability management programs.     

Bilateral pressure pain sensitivity mapping of the temporalis muscle in chronic tension-type headache

Purpose.— To analyze pressure pain sensitivity maps in chronic tension-type headache (CTTH) and healthy controls over nine locations covering the temporalis muscle.
Background.— Lower pressure pain thresholds (PPT) have been found in craniofacial muscles in patients with CTTH. Since the temporalis muscle can play a relevant role in the genesis or maintenance of headache, the determination of pressure pain sensitivity maps of this muscle is needed.
Methods.— A pressure algometer was used to measure PPT over 9 points of the temporalis muscle (3 points in the anterior part of the muscle, another 3 in the middle of the muscle, and the remaining 3 in the posterior part) in 15 females suffering from CTTH and 10 healthy women. A pressure pain sensitivity map of both dominant and nondominant sides in patients and controls was calculated.
Results.— Chronic tension-type headache patients showed lower PPT as compared with healthy subjects ( P  < .01). Further, PPT levels of the nondominant side were lower than those on the dominant side for controls ( P  < .01). Within the CTTH group, more bilaterally homogeneous pressure pain sensitivity maps with PPT decreased from the posterior to anterior column were found, whereas among controls, PPT distribution maps were inhomogeneous with side-to-side differences.
Conclusions.— Our data may provide preliminary new key information about muscle sensitivity, since it seems that pressure pain sensitivity maps could be different between CTTH patients and healthy subjects. Further studies with greater sample sizes and other headache populations are now required to confirm our results.     

Asians differ from non‐Hispanic Whites in experimental pain sensitivity

This study examined differences between Asians and non‐Hispanic Whites (Whites) in pain sensitivity, and its relationship to mean arterial pressure (MAP) and heart rate (HR). In 30 Whites (50% female) and 30 Asians (50% female), experimental pain sensitivity was assessed with a hand cold pressor task, yielding measures of pain threshold, tolerance, intensity, and unpleasantness. Mean arterial pressure and HR measurements taken at rest and in response to speech stress were assessed. Perceived stress, anxiety, perfectionism, parental criticism, parental expectations and depressive symptoms were also measured. The results indicated that for the cold pain test, Asians demonstrated significantly lower pain threshold and tolerance levels than Whites. Although no ethnic differences were seen for MAP or HR responses to stress, for Whites higher stress MAP levels were correlated with reduced pain sensitivity, while for Asians higher baseline and stress HR levels were correlated with reduced pain sensitivity. Asians reported higher parental expectations and greater parental criticism than Whites. For Asians only, higher levels of perfectionism were related to more depressive symptoms, anxiety and perceived stress. These results indicate that Asian Americans are more sensitive to experimental pain than Whites and suggest ethnic differences in endogenous pain regulatory mechanisms (e.g. MAP and HR). The results may also have implications for understanding ethnic differences in clinical pain.     

Quality of life in chronic pain is more associated with beliefs about pain, than with pain intensity.

OBJECTIVES: The objectives of this study were to investigate pain cognitions and quality of life of chronic pain patients referred to a multi-disciplinary university pain management clinic and to search for predictors of quality of life. METHODS: A heterogeneous group of 1208 chronic pain patients referred to the Maastricht university hospital pain clinic participated in this cross-sectional study. At the initial assessment, all patients completed a set of questionnaires on demographic variables, cause, location, pain intensity (McGill pain questionnaire, MPQ), pain coping and beliefs (pain coping and cognition list, PCCL), pain catastrophising (pain catastrophising scale, PCS) and eight dimensions of quality of life (Rand-36). RESULTS: The results showed that the present sample of heterogeneous pain patients reported low quality of life on each domain and significantly lower scores than has been found in previous studies with other Dutch chronic pain populations. Patients with low back pain and multiple pain localisations experienced most functional limitations. Women reported more pain, more catastrophising thoughts about pain, more disability and lower vitality and general health. When tested in a multiple regression analysis, pain catastrophising turned out to be the single most important predictor of quality of life. Especially social functioning, vitality, mental health and general health are significantly associated with pain catastrophising. CONCLUSIONS: Patients from a multi-disciplinary university pain clinic experience strikingly low quality of life, whereby low back pain patients and patients with multiple pain localisations have the lowest quality of life. Pain catastrophising showed the strongest association with quality of life, and stronger than pain intensity.     

Stretch reflex and pressure pain thresholds in chronic tension-type headache patients and healthy controls

To compare the jaw-stretch reflex and pressure pain thresholds (PPT) in chronic tension-type headache (CTTH) patients and healthy controls, 30 patients (15 male and 15 female) and 30 age- and sex-matched healthy subjects were investigated. Stretch reflexes were recorded in the temporalis and masseter muscles and PPT was determined in the anterior temporalis, splenius capitis and masseter muscles. The results showed that the amplitude of the stretch reflex in CTTH patients was higher compared with control subjects ( P  < 0.045), and higher in women compared with men in the right and left anterior temporalis muscles ( P  < 0.009). There were no differences in the PPT value between CTTH and control subjects ( P  > 0.509), whereas women showed significantly lower PPT measurements ( P  < 0.046). The results demonstrated a facilitation of the stretch reflex pathways in CTTH patients that is unrelated to measures of pericranial sensitivity.     

Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans

The tyrosine kinase receptor c-Kit is critically involved in the modulation of nociceptive sensitivity in mice. Ablation of the c-Kit gene results in hyposensitivity to thermal pain, whereas activation of c-Kit produces hypersensitivity to noxious heat, without altering sensitivity to innocuous mechanical stimuli. In this study, we investigated the role of c-Kit signaling in human pain perception. We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit but also Abl1, PDFGFRα, and PDFGFRβ, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. We examined 31 asymptomatic CML patients (14 male and 17 female) receiving Imatinib/Nilotinib treatment and compared them to 39 age- and sex-matched healthy controls (12 male and 27 female). We used cutaneous heat and cold stimulation to test normal and noxious thermal sensitivity, and a grating orientation task to assess tactile acuity. Thermal pain thresholds were significantly increased in the Imatinib/Nilotinib-treated group, whereas innocuous thermal and tactile thresholds were unchanged compared to those in the control group. In conclusion, our findings suggest that the biological effects of c-Kit inhibition are comparable in mice and humans in that c-Kit activity is required to regulate thermal pain sensitivity but does not affect innocuous thermal and mechanical sensation. The effect on experimental heat pain observed in our study is comparable to those of several common analgesics; thus modulation of the c-Kit pathway can be used to specifically modulate noxious heat and cold sensitivity in humans.     

Glutamate and prostaglandin E2 in the trapezius muscle of female subjects with chronic muscle pain and controls determined by microdialysis.

Much is still unknown concerning the mechanisms underlying the development of chronic muscle pain. The presence and magnitude of inflammatory substances and neurotransmitters in chronic painful conditions is not clear. The aims of the present study were to determine, with the use of microdialysis, the interstitial concentrations and the equilibration times for PGE2 and glutamate in the trapezius muscles of nine female subjects with chronic muscle pain, and nine pain-free age-matched controls. A microdialysis probe was implanted in the upper part of the trapezius muscle and perfused with Ringer-acetate solution at a flow rate of 0.3 microL/min. Samples were obtained every 30 min, during a 4-h rest period. At equilibration, the mean concentrations (+/-SE) of PGE2 were 0.71 (+/-0.11) ng/mL for the pain-group and 0.97 (+/-0.35) ng/mL for the controls. For glutamate the mean concentrations for the pain-group were 66.3 (+/-13.3) micromol/L and 60.6 (+/-22.9) micromol/L for the controls. For the pain group and the control group, respectively, equilibration for PGE2 was reached at 180 and 150 min, and for glutamate at 150 and 120 min. The present study showed no differences between groups in the concentrations of PGE2 and glutamate in the trapezius muscle. Further, it revealed that when using the slow-flow method, a period of at least 2.0-2.5 h is needed, after probe insertion, to reach steady state for glutamate and PGE2.