Specifying the nonspecific components of acupuncture analgesia

It is well known that acupuncture has pain-relieving effects, but the contribution of specific and especially nonspecific factors to acupuncture analgesia is less clear. One hundred one patients who developed pain of ?3 on a visual analog scale (VAS, 0 to 10) after third molar surgery were randomized to receive active acupuncture, placebo acupuncture, or no treatment for 30 min with acupuncture needles with potential for double-blinding. Patients’ perception of the treatment (active or placebo) and expected pain levels (VAS) were assessed before and halfway through the treatment. Looking at actual treatment allocation, there was no specific effect of active acupuncture (P = .240), but there was a large and significant nonspecific effect of placebo acupuncture (P < .001), which increased over time. Interestingly, however, looking at perceived treatment allocation, there was a significant effect of acupuncture (P < .001), indicating that patients who believed they received active acupuncture had significantly lower pain levels than those who believed they received placebo acupuncture. Expected pain levels accounted for significant and progressively larger amounts of the variance in pain ratings after both active and placebo acupuncture (up to 69.8%). This is the first study to show that under optimized blinding conditions, nonspecific factors such as patients’ perception of and expectations toward treatment are central to the efficacy of acupuncture analgesia and that these factors may contribute to self-reinforcing effects in acupuncture treatment. To obtain an effect of acupuncture in clinical practice, it may therefore be important to incorporate and optimize these factors.     

Sleep restriction attenuates amplitudes and attentional modulation of pain-related evoked potentials,but augments pain ratings in healthy volunteers

The experiment investigated the impact of sleep restriction on pain perception and related evoked potential correlates (laser-evoked potentials, LEPs). Ten healthy subjects with good sleep quality were investigated in the morning twice, once after habitual sleep and once after partial sleep restriction. Additionally, we studied the impact of attentional focussing on pain and LEPs by directing attention to (intensity discrimination) or away from the stimulus (mental arithmetic). Laser stimuli directed to the hand dorsum were rated as 30% more painful after sleep restriction (49 ± 7 mm) than after a night of habitual sleep (38 ± 7 mm). A significant interaction between attentional focus and sleep condition suggested that attentional focusing was less distinctive under sleep restriction. Intensity discrimination was preserved. In contrast, the amplitude of the early parasylvian N1 of LEPs was significantly smaller after a night of partial sleep restriction (−36%, p < 0.05). Likewise, the amplitude of the vertex N2–P2 was significantly reduced (−34%, p < 0.01); also attentional modulation of the N2–P2 was reduced. Thus, objective (LEPs) and subjective (pain ratings) parameters of nociceptive processing were differentially modulated by partial sleep restriction. We propose, that sleep reduction leads to an impairment of activation in the ascending pathway (leading to reduced LEPs). In contradistinction, pain perception was boosted, which we attribute to lack of pain control distinct from classical descending inhibition, and thus not affecting the projection pathway. Sleep-restricted subjects exhibit reduced attentional modulation of pain stimuli and may thus have difficulties to readily attend to or disengage from pain.     

Perceptual bias in pain: A switch looks closer when it will relieve pain than when it won’t

Pain is fundamental to survival, as are our perceptions of the environment. It is often assumed that we see our world as a read-out of the sensory information that we receive; yet despite the same physical makeup of our surroundings, individuals perceive differently. What if we “see” our world differently when we experience pain? Until now, the causal effect of experimental pain on the perception of an external stimulus has not been investigated. Eighteen (11 female) healthy volunteers participated in this randomised repeated-measures experiment, in which participants estimated the distance to a switch placed on the table in front of them. We varied whether or not the switch would instantly stop a stimulus, set to the participant’s pain threshold, being delivered to their hand, and whether or not they were required to reach for the switch. The critical result was a strong interaction between reaching and pain [F(1, 181) = 4.8, P = 0.03], such that when participants experienced pain and were required to reach for a switch that would turn off the experimental stimulus, they judged the distance to that switch to be closer, as compared to the other 3 conditions (mean of the true distance 92.6%, 95% confidence interval 89.7%–95.6%). The judged distance was smaller than estimates in the other 3 conditions (mean ± SD difference >5.7% ± 2.1%, t(181) >3.5, P < 0.01 for all 3 comparisons). We conclude that the perception of distance to an object is modulated by the behavioural relevance of the object to ongoing pain.     

Peripheral opioid receptor blockade increases postoperative morphine demands—A randomized,double-blind,placebo-controlled trial

Experimental studies suggest that a large proportion of opioid analgesia can be mediated by peripheral opioid receptors. This trial examined the contribution of such receptors to clinical analgesia induced by intravenous morphine. We hypothesized that the selective blockade of peripheral opioid receptors by methylnaltrexone (MNX) would increase the patients’ demand for morphine to achieve satisfactory postoperative pain relief. In a double-blind, placebo-controlled, sequential 2-center trial, 50 patients undergoing knee replacement surgery were randomized (1:1) to receive either subcutaneous MNX (0.9 mg/kg) (hospital I: n = 14; hospital II: n = 11) or saline (hospital I: n = 13; hospital II: n = 12) at the end of surgery. The primary endpoint was the cumulative amount of intravenous morphine administered during the first 8 hours. Secondary endpoints were pain scores at rest and during movement (by numerical rating scale and McGill Questionnaire), vital signs, adverse side effects, and withdrawal symptoms. After MNX, demands for morphine were strongly (by about 40%) increased (hospital I: 35.31 ± 12.99 mg vs 25.51 ± 7.92 mg, P = 0.03; hospital II: 35.42 ± 11.73 mg vs 24.80 ± 7.84 mg, P = 0.02; pooled data: P < .001; means ± SD). Secondary endpoints were similar in all groups (P > .05). Thus, a significant proportion of analgesia produced by systemically administered morphine is mediated by peripheral opioid receptors. Drugs that selectively activate such receptors should have the potential to produce powerful clinical pain relief.     

Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1

Complex Regional Pain Syndrome Type 1 (CRPS-1) responds poorly to standard pain treatment. We evaluated if the N-methyl-d-aspartate receptor antagonist S(+)-ketamine improves pain in CRPS-1 patients. Sixty CRPS-1 patients (48 females) with severe pain participated in a double-blind randomized placebo-controlled parallel-group trial. Patients were given a 4.2-day intravenous infusion of low-dose ketamine (n = 30) or placebo (n = 30) using an individualized stepwise tailoring of dosage based on effect (pain relief) and side effects (nausea/vomiting/psychomimetic effects). The primary outcome of the study was the pain score (numerical rating score: 0–10) during the 12-week study period. The median (range) disease duration of the patients was 7.4 (0.1–31.9) years. At the end of infusion, the ketamine dose was 22.2 ± 2.0 mg/h/70 kg. Pain scores over the 12-week study period in patients receiving ketamine were significantly lower than those in patients receiving placebo (P < 0.001). The lowest pain score was at the end of week 1: ketamine 2.68 ± 0.51, placebo 5.45 ± 0.48. In week 12, significance in pain relief between groups was lost (P = 0.07). Treatment did not cause functional improvement. Patients receiving ketamine more often experienced mild to moderate psychomimetic side effects during drug infusion (76% versus 18%, P < 0.001). In conclusion, in a population of mostly chronic CRPS-1 patients with severe pain at baseline, a multiple day ketamine infusion resulted in significant pain relief without functional improvement. Treatment with ketamine was safe with psychomimetic side effects that were acceptable to most patients.     

Increased basal mechanical pain sensitivity but decreased perceptual wind-up in a human model of relative hypocortisolism

Clinical data have accumulated showing that relative hypocortisolism, which may be regarded as a neuroendocrinological correlate of chronic stress, may be a characteristic of some functional pain syndromes. However, it has not been clarified yet whether deregulations of the hypothalamus–pituitary–adrenal (HPA) axis may directly alter pain perception and thus be causally involved in the pathophysiology of these disorders. To test this hypothesis, we performed a randomized placebo-controlled crossover trial in N = 20 healthy drug-free volunteers (median age 24 yrs) and analyzed the effects of metyrapone-induced hypocortisolism on quantitatively assessed basal mechanical pain sensitivity (1.5–13 m/s impact stimuli), perceptual wind-up (9 m/s impact stimuli at 1 Hz) and temporal summation of pain elicited by inter-digital web pinching (IWP; 10 N pressure stimuli for 2 min). Experimentally induced hypocortisolism significantly decreased pain detection thresholds and augmented temporal summation of IWP-induced pain (p < .05). The latter effect was dependent on the relative reduction in cortisol levels, and seemed to rely on a potentiated sensitization and not merely on the observed changes in basal pain sensitivity. Perceptual wind-up by contrast was reduced when cortisol synthesis was blocked (p < .05). This result is reminiscent of findings from animal studies showing a reversal of NMDA receptor activation by glucocorticoid receptor antagonists in neuropathic pain models. Our results speak in favor of a potential causal role of HPA axis alterations in pain chronicity.     

Validation and properties of the verbal numeric scale in children with acute pain

Although the verbal numeric scale (VNS) is used frequently at patients’ bedsides, it has never been formally validated in children with acute pain. In order to validate this scale, a prospective cohort study was performed in children between 8 and 17 years presenting to a pediatric emergency department (ED) with acute pain. Pain was graded using the VNS, the visual analogue scale (VAS), and the verbal rating scale (VRS). A second assessment was done before discharge. We determined a priori that in order to be valid, the VNS would need to: correlate with the VAS (concurrent validity); decrease after intervention to reduce pain (construct validity); and be associated with the VRS categories (content validity). The VNS interchangeability with the VAS, its minimal clinically significant difference, and test–retest reliability were also determined. A total of 202 patients (mean age: 12.2 ± 2.6 years) were enrolled. The VNS correlated with the VAS: r_ic = 0.93, p < 0.001. There were differences in the VNS before versus after interventions (p < 0.001), and between VRS categories (mild versus moderate, p < 0.001; moderate versus severe, p < 0.001). The 95% limits of agreement (interchangeability) between VNS/VAS were outside the a priori set limit of ±2.0: −1.8, 2.5. The VNS minimal clinically significant difference was 1. The VNS had good test–retest reliability with 95% limits of agreement of −0.9 and 1.2. In conclusion, the VNS provides a valid and reliable scale to evaluate acute pain in children aged 8–17 years but is not interchangeable with the VAS.     

Hyperalgesia and functional sensory loss in restless legs syndrome

Pain and other sensory signs in patients with restless legs syndrome (RLS) are still poorly understood, as most investigations focus on motor system dysfunctions. This study aimed to investigate somatosensory changes in patients with primary RLS and the restoration of somatosensory function by guideline-based treatment. Forty previously untreated RLS patients were investigated unilaterally over hand and foot using quantitative sensory testing (QST) and were compared with 40 age- and gender-matched healthy subjects. The predominant finding in RLS patients was 3- to 4-fold increase of sensitivity to pinprick stimuli in both extremities (hand: P < .05; foot: P < .001), a sensory pathway involved in withdrawal reflexes. Pinprick hyperalgesia was not paralleled by dynamic mechanical allodynia. Additional significant sensory changes were tactile hypoesthesia in both extremities (hand: P < .05; foot P < .01) and dysesthesia to non-noxious cold stimuli (paradoxical heat sensation), which was present in the foot in an unusually high proportion (14 of 40 patients; P < .01). In 8 patients, follow-up QST 2 to 20 months after treatment with l-DOPA (L-3,4-dihydroxyphenylalanine) revealed a significant reduction of pinprick hyperalgesia (−60%, P < .001), improved tactile detection (+50%, P < .05), and disappearance of paradoxical heat sensation in half of the patients. QST suggested a type of spinal or supraspinal central sensitization differing from neuropathic pain or human experimental models of central sensitization by the absence of dynamic mechanical allodynia. Reversal of pinprick hyperalgesia by l-DOPA may be explained by impaired descending inhibitory dopaminergic control on spinal nociceptive neurons. Restoration of tactile sensitivity and paradoxical heat sensations suggest that they were functional disturbances resulting from central disinhibition.     

Pain in chemotherapy-induced neuropathy – More than neuropathic?

Chemotherapy-induced neuropathy (CIN) is an adverse effect of chemotherapy. Pain in CIN might comprise neuropathic and nonneuropathic (ie, musculoskeletal) pain components, which might be characterized by pain patterns, electrophysiology, and somatosensory profiling. Included were 146 patients (100 female, 46 male; aged 56 ± 0.8 years) with CIN arising from different chemotherapy regimens. Patients were characterized clinically through nerve conduction studies (NCS) and quantitative sensory testing (QST). Questionnaires for pain (McGill) and anxiety/depression (Hospital Anxiety and Depression Scale) were supplied. Patients were followed-up after 17 days. Large- (61%) and mixed- (35%) fibre neuropathies were more frequent than small-fibre neuropathy (1.4%). The 5 major chemotherapeutic regimens impacted differently on large- but not on small-fibre function and did not predict painfulness. Chronic pain associated with CIN was reported in 41.7%. Painless and painful CIN did not differ in QST profiles or electrophysiological findings, but different somatosensory patterns were found in CIN subgroups (pain at rest [RestP], n = 25; movement-associated pain [MovP], n = 15; both pain characteristics [MovP+RestP], n = 21; or no pain [NonP], n = 85): small-fibre function (cold-detection threshold, CDT: z score: −1.46 ± 0.21, P < 0.01) was most impaired in RestP; mechanical hyperalgesia was exclusively found in MovP (z score: +0.81 ± 0.30, P < 0.05). “Anxiety” discriminated between painful and painless CIN; “CDT” and “anxiety” discriminated between patients with ongoing (RestP) and movement-associated pain (MovP) or pain components (MovP+RestP). The detrimental effect of chemotherapy on large fibres failed to differentiate painful from painless CIN. Patients stratified for musculoskeletal or neuropathic pain, however, differed in psychological and somatosensory parameters. This stratification might allow for the application of a more specific therapy.     

One night of total sleep deprivation promotes a state of generalized hyperalgesia: A surrogate pain model to study the relationship of insomnia and pain

Sleep disturbances are highly prevalent in chronic pain patients. Understanding their relationship has become an important research topic since poor sleep and pain are assumed to closely interact. To date, human experimental studies exploring the impact of sleep disruption/deprivation on pain perception have yielded conflicting results. This inconsistency may be due to the large heterogeneity of study populations and study protocols previously used. In addition, none of the previous studies investigated the entire spectrum of nociceptive modalities. To address these shortcomings, a standardized comprehensive quantitative sensory protocol was used in order to compare the somatosensory profile of 14 healthy subjects (6 female, 8 male, 23.5 ± 4.1 year; mean ± SD) after a night of total sleep deprivation (TSD) and a night of habitual sleep in a cross-over design. One night of TSD significantly increased the level of sleepiness (P < 0.001) and resulted in higher scores of the State Anxiety Inventory (P < 0.01). In addition to previously reported hyperalgesia to heat (P < 0.05) and blunt pressure (P < 0.05), study participants developed hyperalgesia to cold (P < 0.01) and increased mechanical pain sensitivity to pinprick stimuli (P < 0.05) but no changes in temporal summation. Paradoxical heat sensations or dynamic mechanical allodynia were absent. TSD selectively modulated nociception, since detection thresholds of non-nociceptive modalities remained unchanged. Our findings show that a single night of TSD is able to induce generalized hyperalgesia and to increase State Anxiety scores. In the future, TSD may serve as a translational pain model to elucidate the pathomechanisms underlying the hyperalgesic effect of sleep disturbances.     

Increased wind-up to heat pain in women with a childhood history of functional abdominal pain

Idiopathic or functional abdominal pain (FAP) is common in school-age children and typically reflects a functional gastrointestinal disorder (FGID). FGIDs in adults have been distinguished by enhanced responses of the central nervous system to pain stimuli, known as central sensitization. This study investigated whether adolescents and young adults with a history of pediatric FAP (n = 144), compared with well control subjects (n = 78), showed enhanced central sensitization demonstrated by greater temporal summation (wind-up) to brief, repetitive heat pulses. We also assessed the role of gender and trait anxiety in wind-up to heat pain. Women with a history of FAP showed greater wind-up to heat pain than men with a history of FAP (P < .05) and well control subjects of both genders (P < .05). Results were similar for FAP participants whose abdominal pain was ongoing at follow-up and those whose pain had resolved. Although anxiety was significantly higher in the FAP group compared with control subjects (P < .01) and in women compared with men (P < .05), anxiety did not explain the increased wind-up observed in women with a childhood history of FAP. Results suggest that women with a pediatric history of FAP may have a long-term vulnerability to pain associated with enhanced central nervous system responses to pain stimuli.     

Hyperfibrinolysis in out of hospital cardiac arrest is associated with markers of hypoperfusion

Aim of the study

This study investigated the incidence of hyperfibrinolysis upon emergency department (ED) admission in patients with out of hospital cardiac arrest (OHCA), and the association of the degree of hyperfibrinolysis with markers of hypoperfusion.

Methods

From 30 OHCA patients, cardiopulmonary resuscitation (CPR) time, pH, base excess (BE), and serum lactate were measured upon ED admission. A 20% decrease of rotational thromboelastometry maximum clot firmness (MCF) was defined as hyperfibrinolysis. Lysis parameters included maximum lysis (ML), lysis onset time (LOT) and lysis index at 30 and 45 min (LI30/LI45). The study was approved by the Human Subjects Committee.

Results

Hyperfibrinolysis was present in 53% of patients. Patients with hyperfibrinolysis had longer median CPR times (36 (15–55) vs. 10 (7–18) min; P = 0.001), a prolonged activated partial thromboplastin time (54 ± 16 vs. 38 ± 10 s; P = 0.006) and elevated D-dimers (6.1 ± 2.1 vs. 2.3 ± 2.0 μg/ml; P = 0.02) when compared to patients without hyperfibrinolysis. Hypoperfusion markers, including pH (6.96 ± 0.11 vs. 7.17 ± 0.15; P < 0.001), base excess (−20.01 ± 3.53 vs. −11.91 ± 6.44; P < 0.001) and lactate (13.1 ± 3.7 vs. 8.0 ± 3.7 mmol/l) were more disturbed in patients with hyperfibrinolysis than in non-hyperfibrinolytic subjects, respectively. The LOT showed a good association with CPR time (r = −0.76; P = 0.003) and lactate (r = −0.68; P = 0.01), and was longer in survivors (3222 ± 34 s) than in non-survivors (1356 ± 833; P = 0.044).

Conclusion

A substantial part of OHCA patients develop hyperfibrinolysis in association with markers for hypoperfusion. Our data further suggest that the time to the onset of clot lysis may be an important marker for the severity of hyperfibrinolysis and patient outcome.     

Enhanced pain modulation among triathletes: A possible explanation for their exceptional capabilities

Triathletes and ironman triathletes engage in an extremely intense sport that involves hours of considerable pain, as well as physical and psychological stress, every day. The basic pain modulation properties of these athletes has not been established and therefore it is not clear whether they present with unique features that enable them to engage in such efforts. The aim was to investigate the existence of possible alterations in pain perception and modulation of triathletes, as well as possible underlying factors. Participants were 19 triathletes and 17 non-athletes who underwent measurement of pain threshold, pain tolerance, suprathreshold perceived pain intensity, temporal summation of pain, and conditioned pain modulation (CPM). Participants also completed the fear of pain and the pain catastrophizing questionnaires, and rated the amount of perceived stress. Triathletes exhibited higher pain tolerance (P < .0001), lower pain ratings (P < .001), and lower fear of pain values (P < .05) than controls. The magnitude of CPM was significantly greater in triathletes (P < .05), and negatively correlated with fear of pain (P < .05) and with perceived mental stress during training and competition (P < .05). The results suggest that triathletes exhibit greater pain tolerance and more efficient pain modulation than controls, which may underlie their perseverance in extreme physical efforts and pain during training/competitions. This capability may be enhanced or mediated by psychological factors, enabling better coping with fear of pain and mental stress.     

Hypertension prevalence and diminished blood pressure–related hypoalgesia in individuals reporting chronic pain in a general population: The Tromsø Study

Resting blood pressure (BP) is inversely related to pain sensitivity in individuals free of chronic pain, reflecting homeostatic interactions between cardiovascular and pain modulatory systems. Several laboratory studies indicate that BP-related hypoalgesia is diminished in chronic pain patients, suggesting dysfunction in these interacting systems. Separate epidemiological findings reveal elevated hypertension prevalence in the chronic pain population. This study for the first time simultaneously evaluated both hypertension prevalence and BP-related hypoalgesia as they relate to chronic pain in the same sample. Resting BP and pain sensitivity were evaluated in a large general population sample (n = 10,135, aged 30–87 years). Subjects participated in a standardized 106 s cold pressor test, providing pain ratings at 9 s intervals. Self-reported presence of chronic pain and history of hypertension and use of antihypertensive medication were assessed. Significant interactions between chronic pain status and resting systolic (P < .001) and diastolic BP (P < .001) on mean pain ratings were observed. These interactions were due to significant (P < .001) BP-related hypoalgesia in individuals free of chronic pain that was twice the magnitude of the hypoalgesia observed in the group reporting chronic pain. Presence of chronic pain was associated with significantly increased odds of comorbid hypertension (P < .001). Within the chronic pain group, higher chronic pain intensity was a significant predictor of positive hypertension status beyond the effects of traditional demographic risk factors (P < .05). Results are consistent with the hypothesis that increased hypertension risk in the chronic pain population might be linked in part to chronic pain–related dysfunction in interacting cardiovascular–pain modulatory systems.     

Dexmedetomidine as an adjunct to epidural analgesia after abdominal surgery in elderly intensive care patients: A prospective, double-blind, clinical trial

Background: The ideal postoperative analgesia management of elderly surgical patients in intensive care units (ICUs) is continually being investigated.Objective: The purpose of this study was to assess the effectiveness and tolerability of IV administration of dexmedetomidine as an adjunct to a low-dose epidural bupivacaine infusion for postoperative analgesia after abdominal surgery in elderly patients in the ICU.Methods: ICU patients aged >70 years undergoing abdominal surgery were eligible for the study. A lumbar epidural catheter was inserted at the beginning of the surgery with no medication. On arrival at the ICU, the catheter was loaded with 0.25% bupivacaine 25 mg at the T8 to T10 sensory level, and a continuous infusion of 0.125% bupivacaine was started at 4 to 6 mL/h in combination with patient-controlled epidural analgesia (PCEA) of fentanyl (4 μg/bolus) for pain treatment. Patients in the treatment group received dexmedetomidine as an IV loading dose of 0.6 pg/kg for 30 minutes followed by continuous infusion at 0.2 μg/kg · h^-1. Patients in the control group were not administered dexmedetomidine. The effectiveness of the pain relief was determined using a visual analog scale (VAS) (0 = no pain to 10 = worst pain imaginable) at rest. VAS score, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure, and arterial blood gases were monitored periodically for 24 hours after surgery. If required, tenoxicam (20-mg IV bolus) was used to ensure a VAS score of ≤3. The number of times PCEA and tenoxicam were administered and the occurrence of adverse events (AEs) were also recorded.Results: Sixty patients (34 men, 26 women; mean [SD] age, 75.96 [4.25] years; mean [SD] weight, 74.13 [10.62] kg) were included in the study. VAS scores were significantly lower in the dexmedetomidine group compared with the control group at hours 1, 2, and 12 (VAS [hour 1]: 2.8 [0.4], P < 0.001; VAS [hour 2]: 2.7 [0.5], P < 0.001; and VAS [hour 12]: 0.9 [0.7], P 0.044). The mean number of administrations of fentanyl via PCEA was significantly greater in the control group compared with the dexmedetomidine group (2.20 vs 6.63 times; P < 0.001). The mean number of administrations of tenoxicam was significantly lower in the treatment group than the control group (0.27 vs 1.07 times; P < 0.001). In the control group, the decreases in sedation at 0, 8, 12, 16, and 20 hours were significant compared with baseline (P = 0.024, P = 0.001, P = 0.020, P < 0.001, and P = 0.005, respectively). Mean HR, SBR and AEs (eg, bradycardia [HR <60 beats/min], respiratory depression [respiratory rate <8 breaths/min], hypotension \SBP <90 mm Hg], oversedation, hypoxia, and hypercapnia) decreased significantly in the dexmedetomidine group (all, P < 0.05). Significantly more patients in the dexmedetomidine group rated their satisfaction with postoperative pain control as excellent compared with the control group (12 vs 6 patients; P = 0.014).Conclusion: Intravenous dexmedetomidine was effective and generally well tolerated as an analgesic adjunct to epidural low-dose bupivacaine infusion for pain treatment, with lower need for opioids after abdominal surgery in these elderly intensive care patients than in the control group.     

The mediating role of pain catastrophizing in the relationship between presurgical anxiety and acute postsurgical pain after hysterectomy

The aim of this study was to examine the joint role of demographic, clinical, and psychological variables as predictors of acute postsurgical pain in women undergoing hysterectomy due to benign disorders. A consecutive sample of 203 women was assessed 24 hours before (T1) and 48 hours after (T2) surgery. Baseline pain and predictors were assessed at T1 and postsurgical pain and analgesic consumption at T2. Several factors distinguished women who had no or mild pain after surgery from those who had moderate to severe pain, with the latter being younger, having more presurgical pain, and showing a less favorable psychological profile. Younger age (odds ratio [OR] = 0.90, P < .001), presurgical pain (OR = 2.50, P <.05), pain due to other causes (OR = 4.39, P = .001), and pain catastrophizing (OR = 3.37, P = .001) emerged as the main predictors of pain severity at T2 in multivariate logistic regression. This was confirmed in hierarchical linear regression (β = −0.187, P < .05; β = 0.146, P < .05; β = 0.136, P < .05; β = 0.245, P < .01, respectively). Presurgical anxiety also predicted pain intensity at T2. Findings revealed an integrative heuristic model that accounts for the joint influence of demographic, clinical, and psychological factors on postsurgical pain intensity and severity. In further mediation analysis, pain catastrophizing emerged as a full mediator between presurgical anxiety and postsurgical pain intensity. The potential clinical implications for understanding, evaluating, and intervening in postsurgical pain are discussed.     

Validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) for monitoring iatrogenic withdrawal syndrome in pediatric patients

Critically ill pediatric patients frequently receive prolonged analgesia and sedation to provide pain relief and facilitate intensive care therapies. Iatrogenic withdrawal syndrome occurs when these drugs are stopped abruptly or weaned too rapidly. We investigated the validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) in children during weaning of analgesics and sedatives. Of 308 children initially supported on mechanical ventilation for acute respiratory failure, 126 (41%) from 21 centers (median age 1.6 years; interquartile range 0.6-7.7 years) were exposed to 5 or more days of opioids. Subjects were assessed for withdrawal symptoms with the WAT-1, an 11-item (12-point) scale, from the first day of weaning from analgesia/sedation until 72 h after the last opioid dose. A total of 836 daily WAT-1 assessments were completed, with a median (interquartile range) WAT-1 score of 2 (0-4) over 6 (3-9) days per subject. There were no significant differences in WAT-1 scores as a function of age. Factor analyses confirmed that motor-related symptoms and behavioral state accounted for the most variance in WAT-1 scores. Supporting construct validity, cumulative opioid exposures were greater [40.2 (19.7-83.4) vs 17.6 (14.6-39.7) mg/kg, P = .004], length of opioid treatment before weaning was longer [7 (6-11) vs 5 (5-8) days, P = .004], and length of weaning from opioids was longer [10 (6-14) vs 6 (3-9) days, P = .008] in subjects with WAT-1 scores of ?3 compared to subjects with WAT-1 scores of <3. The WAT-1 shows good psychometric performance and generalizability when used to assess clinically important withdrawal symptoms in pediatric intensive care and general ward settings.     

‘Pain inhibits pain’ mechanisms: Is pain modulation simply due to distraction?

‘Diffuse noxious inhibitory controls’ (DNIC), a form of supraspinal descending endogenous analgesia, requires a noxious conditioning stimulus for pain attenuation. This may be partly dependent on a distraction effect. The term “conditioned pain modulation” (CPM) has recently been introduced to describe the psychophysical paradigm to test DNIC. The present study aimed to determine whether distraction and tonic heat stimulation inhibit pain through the same or different mechanisms by looking at whether there is a similar or even an additive effect on pain attenuation. Test pain was brief heat stimulation applied to the left volar of 34 healthy volunteers. For conditioning, the right hand was immersed in 46.5 °C water. Distraction was provided by three different difficulty levels of continuous cognitive visual tasks. Experimental blocks consisted of test pain: (1) alone; ‘baseline’, (2) with conditioning pain; ‘CPM’, (3) with distraction; ‘distraction’ and (4) with conditioning pain and distraction; ‘combined’. They were randomized and repeated three times and pain intensity and unpleasantness rated. Results showed an overall effect of experimental block on test pain intensity (P = 0.0125). Post-hoc tests revealed a significant reduction in pain intensity ratings under Combined (21.2 ± 2.3; mean ± SEM) compared to CPM alone (16.0 ± 2.3) (P < 0.05). Furthermore, at all levels of distraction there were always a few subjects who were not distracted despite expressing CPM. Based on the additive effect of CPM and distraction on pain inhibition, and the cases of no distraction despite CPM, we suggest that CPM acts independently from distraction.     

Central hyperexcitability as measured with nociceptive flexor reflex threshold in chronic musculoskeletal pain: a systematic review

Chronic musculoskeletal conditions are increasingly conceived as involving altered central nervous system processing, and impaired nociceptive flexor reflex (NFR) appears to reflect altered central nervous system processing. The primary objective was to synthesize the evidence for impaired NFR in these conditions. The secondary objective was to evaluate the NFR stimuli parameters employed by reviewed studies. Electronic databases: MEDLINE, CINAHL, Embase, PEDro, Google Scholar, and Cochrane library were searched from the mid-1960s to June 2010. Experimental reports were systematically reviewed and meta-analysis (where possible) was performed. NFR thresholds and parameters of NFR stimuli were extracted. Sixteen trials were identified, 11 of which were suitable for inclusion in the meta-analysis. Compared to healthy controls, standardized mean differences in NFR threshold were significantly lower in subjects with primary headache (−0.45; 95% confidence interval [CI] −0.77 to −0.13, P = 0.005), fibromyalgia (−0.63; 95% CI −0.93 to −0.34, P < 0.0001), knee pain (−1.51; 95% CI −2.10 to −0.93, P < 0.00001) and whiplash (−0.73; 95% CI −1.11 to −0.35, P = 0.0002). Employed stimuli parameters vary between studies, with inter-pulse duration (P = 0.044) being identified by multiple regression analysis as independent predictors of the variability in NFR threshold in healthy controls. The results indicate that there is evidence of central hyperexcitability in people with chronic musculoskeletal pain. Our review also suggests that shorter inter-pulse duration tends to yield smaller variability in NFR threshold. However, further research investigating optimal stimulation parameters is still warranted.     

Quantitative sensory testing somatosensory profiles in patients with cervical radiculopathy are distinct from those in patients with nonspecific neck–arm pain

The aim of this study was to establish the somatosensory profiles of patients with cervical radiculopathy and patients with nonspecific neck–arm pain associated with heightened nerve mechanosensitivity (NSNAP). Sensory profiles were compared to healthy control (HC) subjects and a positive control group comprising patients with fibromyalgia (FM). Quantitative sensory testing (QST) of thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimulation was performed in the maximal pain area, the corresponding dermatome and foot of 23 patients with painful C6 or C7 cervical radiculopathy, 8 patients with NSNAP in a C6/7 dermatomal pain distribution, 31 HC and 22 patients with FM. For both neck–arm pain groups, all QST parameters were within the 95% confidence interval of HC data. Patients with cervical radiculopathy were characterised by localised loss of function (thermal, mechanical, vibration detection P < .009) in the maximal pain area and dermatome (thermal detection, vibration detection, pressure pain sensitivity P < .04), consistent with peripheral neuronal damage. Both neck–arm pain groups demonstrated increased cold sensitivity in their maximal pain area (P < .03) and the foot (P < .009), and this was also the dominant sensory characteristic in patients with NSNAP. Both neck–arm pain groups differed from patients with FM, the latter characterised by a widespread gain of function in most nociceptive parameters (thermal, pressure, mechanical pain sensitivity P < .027). Despite commonalities in pain characteristics between the 2 neck–arm pain groups, distinct sensory profiles were demonstrated for each group.