PAIN® - Articles in Press

Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin - Corrected Proof

Nicole M.E. Carmichael, Jonathan O. Dostrovsky, Milton P. Charlton — 2010-03-11

Abstract: Release of inflammatory pain mediators from peripheral sensory afferent endings contributes to the development of a positive feedback cycle resulting in chronic inflammation and pain. Botulinum neurotoxin type A (BoNT-A) blocks exocytosis of neurotransmitters and may therefore block the release of pain modulators in the periphery. Subcutaneous administration of BoNT-A (2.5, 5 and 10U) reduced plasma extravasation (PE) caused by electrical stimulation of the saphenous nerve or capsaicin in the rat hindpaw skin (ANOVA, Post hoc Tukey, p<0.05, n=6). Subcutaneous BoNT-A also reduced blood flow changes evoked by saphenous nerve stimulation (ANOVA, Post hoc Tukey, p<0.05, n=6). Subcutaneous BoNT-A had no effect on PE induced by local injection of substance P (SP) or vasodilation induced by local CGRP injection. Although BoNT-A is an effective treatment for a wide range of painful conditions, the toxin’s large size necessitates that it be injected at numerous sites. We found that a short synthetic peptide (TD-1) can facilitate effective transdermal delivery of BoNT-A through intact skin. Coadministration of TD-1 and BoNT-A to the hindpaw skin resulted in a significant reduction in PE evoked by electrical stimulation. The findings show that BoNT-A can be administered subcutaneously or topically with a novel transdermal delivery peptide to reduce inflammation produced by activating nociceptors in the skin. Peptide-mediated delivery of BoNT-A is an easy and non-invasive way of administering the toxin that may prove to be useful in clinical practice.

Macrophage inflammatory protein-1α mediates the development of neuropathic pain following peripheral nerve injury through interleukin-1β up-regulation - Corrected Proof

2010-03-11

Abstract: In the present study, we investigated the role of the macrophage inflammatory protein-1α (MIP-1α) in the pathogenesis of neuropathic pain following partial sciatic nerve ligation (PSL) in mice. MIP-1α mRNA and its protein were dramatically up-regulated after PSL, and MIP-1α was localized on macrophages and Schwann cells in the injured sciatic nerve (SCN). PSL-induced long-lasting tactile allodynia and thermal hyperalgesia were prevented by the perineural injection of anti-MIP-1α (2ng). Intraneural (20ng) and perineural (100ng) injection of recombinant MIP-1α elicited tactile allodynia and thermal hyperalgesia in sham-operated limb. MIP-1α receptors (CCR1 and CCR5) mRNA and their proteins were also up-regulated in the SCN after PSL, and were localized on macrophages and Schwann cells. PSL-induced tactile allodynia was attenuated by perineural injection (0.2nmol) of siRNA against CCR1 and CCR5. On the other hand, PSL-induced thermal hyperalgesia was prevented by siRNA against CCR5, but not CCR1. Interleukin-1β (IL-1β) mRNA and its precursor protein in macrophages and Schwann cells were also up-regulated in the SCN after PSL, and PSL-induced neuropathic pain was prevented by the perineural injection of anti-IL-1β (2ng). PSL-induced IL-1β up-regulation was suppressed by anti-MIP-1α and siRNA against CCR1 and CCR5. Perineural injection of nicotine (20nmol), a macrophage suppressor, prevented PSL-induced neuropathic pain and suppressed MIP-1α and IL-1β expressions. In conclusion, we propose a novel critical molecule MIP-1α derived from macrophages and Schwann cells that appears to play a crucial role in the development of neuropathic pain induced by PSL.

Bright light activates a trigeminal nociceptive pathway - Corrected Proof

Keiichiro Okamoto, Akimasa Tashiro, Zheng Chang, David A. Bereiter — 2010-03-08

Abstract: Bright light can cause ocular discomfort and/or pain; however, the mechanism linking luminance to trigeminal nerve activity is not known. In this study we identify a novel reflex circuit necessary for bright light to excite nociceptive neurons in superficial laminae of trigeminal subnucleus caudalis (Vc/C1). Vc/C1 neurons encoded light intensity and displayed a long delay (>10s) for activation. Microinjection of lidocaine into the eye or trigeminal root ganglion (TRG) inhibited light responses completely, whereas topical application onto the ocular surface had no effect. These findings indicated that light-evoked Vc/C1 activity was mediated by an intraocular mechanism and transmission through the TRG. Disrupting local vasomotor activity by intraocular microinjection of the vasoconstrictive agents, norepinephrine or phenylephrine, blocked light-evoked neural activity, whereas ocular surface or intra-TRG microinjection of norepinephrine had no effect. Pupillary muscle activity did not contribute since light-evoked responses were not altered by atropine. Microinjection of lidocaine into the superior salivatory nucleus diminished light-evoked Vc/C1 activity and lacrimation suggesting that increased parasympathetic outflow was critical for light-evoked responses. The reflex circuit also required input through accessory visual pathways since both Vc/C1 activity and lacrimation were prevented by local blockade of the olivary pretectal nucleus. These findings support the hypothesis that bright light activates trigeminal nerve activity through an intraocular mechanism driven by a luminance-responsive circuit and increased parasympathetic outflow to the eye.

Peripheral endothelin B receptor agonist-induced antinociception involves endogenous opioids in mice - Corrected Proof

Phuong N. Quang, Brian L. Schmidt — 2010-03-08

Abstract: Endothelin-1 (ET-1) produced by various cancers is known to be responsible for inducing pain. While ET-1 binding to ETAR on peripheral nerves clearly mediates nociception, effects from binding to ETBR are less clear. The present study assessed the effects of ETBR activation and the role of endogenous opioid analgesia in carcinoma pain using an orthotopic cancer pain mouse model. mRNA expression analysis showed that ET-1 was nearly doubled while ETBR was significantly down-regulated in a human oral SCC cell line compared to normal oral keratinocytes (NOK). Squamous cell carcinoma (SCC) cell culture treated with an ETBR agonist (10−4M, 10−5M, and 10−6 M BQ-3020) significantly increased the production of β-endorphin without any effects on leu-enkephalin or dynorphin. Cancer inoculated in the hind paw of athymic mice with SCC induced significant pain, as indicated by reduction of paw withdrawal thresholds in response to mechanical stimulation, compared to sham-injected and NOK-injected groups. Intratumor administration of 3mg/kg BQ-3020 attenuated cancer pain by approximately 50% up to 3h post-injection compared to PBS-vehicle and contralateral injection, while intratumor ETBR antagonist BQ-788 treatment (100 and 300μg/kg and 3mg/kg) had no effects. Local naloxone methiodide (500μg/kg) or selective μ-opioid receptor antagonist (CTOP, 500μg/kg) injection reversed ETBR agonist-induced antinociception in cancer animals. We propose that these results demonstrate that peripheral ETBR agonism attenuates carcinoma pain by modulating β-endorphins released from the SCC to act on peripheral opioid receptors found in the cancer microenvironment.

Relationships among alexithymia and pain intensity, pain interference, and vitality in persons with neuromuscular disease: Considering the effect of negative affectivity - Corrected Proof

2010-03-08

Abstract: Alexithymia, the inability to identify or label emotions, has been shown to be associated with pain in patients with a number of chronic pain conditions. We sought to: (1) replicate this association in samples of persons with chronic pain secondary to neuromuscular disease, (2) extend this finding to other important pain-related measures, and (3) to determine whether relationships among alexithymia and study variables existed after controlling for negative affect. One hundred and twenty-nine individuals with muscular dystrophy and chronic pain were administered measures of alexithymia (Toronto Alexithymia Scale, TAS-20), pain intensity (0–10 NRS), pain interference (Brief Pain Inventory Interference scale), mental health (SF-36 Mental Health scale; as a proxy measure of negative affect) and vitality (SF-36 Vitality scale). Higher TAS scores were associated significantly with higher pain intensity and interference, and less vitality. Although the strengths of these associations were reduced when mental health was used as a control, the associations between the Difficulty Identifying Feelings scale and vitality, and the Externally Oriented Thinking and Total TAS scales and pain intensity remained statistically significant. The findings replicate and extend previous findings concerning the associations between alexithymia and important pain-related variables in a sample of persons with chronic pain and neuromuscular disease. Future research is needed to determine the extent to which the associations are due to (1) a possible causal effect of alexithymia on patient functioning that is mediated via its effects on negative affect or (2) the possibility that alexithymia/outcome relationships reflect response bias caused by general negative affectivity.

A response to Wasan editorial “Spinal cord stimulation in a workers’ compensation population: How difficult it can be to interpret a clinical trial”: Stimulating discussion - Corrected Proof

Judith A. Turner, William Hollingworth, Bryan A. Comstock, Richard A. Deyo — 2010-03-08

We thank Dr. Ajay Wasan for his kind comments regarding our article . We wish to respond to a few points raised in the editorial. Regarding Dr. Wasan’s concern about including opioid medication use in the primary composite outcome measure, we note that we also presented the results separately for the individual measures of pain intensity and function, and that the results and conclusions were similar: no difference between the spinal cord stimulation (SCS) group and the pain clinic and usual care groups at 12 or 24months.

The audacity of scope - Corrected Proof

Kenneth M. Prkachin — 2010-03-08

The psychology of pain has been a thriving field for nearly four decades. Numerous contributions toward understanding the determinants of pain experience and managing suffering across the lifespan have been made. It is now an article of faith that psychological factors ranging from learning experiences through cognitive transformations to social processes play important roles in the response to tissue damage and bodily injury.

Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations - Corrected Proof

2010-03-08

Abstract: There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions. An IMMPACT consensus meeting was therefore convened to identify the critical research design considerations for confirmatory chronic pain trials and to make recommendations for their conduct. We present recommendations for the major components of confirmatory chronic pain clinical trials, including participant selection, trial phases and duration, treatment groups and dosing regimens, and types of trials. Increased attention to and research on the methodological aspects of confirmatory chronic pain clinical trials has the potential to enhance their assay sensitivity and ultimately provide more meaningful evaluations of treatments for chronic pain.

Adult attachment and pain catastrophizing for self and significant other - Corrected Proof

Lachlan A. McWilliams, Diane Holmberg — 2010-03-08

Abstract: A growing body of research indicates that attachment insecurity is associated with pain-related catastrophizing. Attachment anxiety has consistently been found to be positively associated with pain catastrophizing. In contrast, the relationship between attachment avoidance and pain catastrophizing has been less consistent. The current study was designed to (a) determine whether anxiety accounts for unique variance in catastrophizing beyond that contributed by the overlapping constructs of self-esteem and neuroticism and (b) clarify the relationship between avoidance and catastrophizing by investigating this relationship when controlling for attachment anxiety. The final objective was to investigate whether attachment is also related to catastrophizing about the pain of significant others. A convenient sample of individuals currently in a romantic relationship (N=148) completed self-report measures of attachment anxiety and avoidance, neuroticism, self-esteem, pain catastrophizing, and significant other pain catastrophizing. Multiple regression analyses indicated that attachment anxiety accounted for unique variance in pain catastrophizing and each of its lower-order components (i.e., rumination, magnification, helplessness), beyond that accounted for by the personality variables. Attachment avoidance was negatively associated with the rumination component of catastrophizing, but this association was only found after controlling for attachment anxiety. The attachment dimensions were also associated with some components of significant other pain catastrophizing. Anxiety was positively associated with the helplessness component of significant other pain catastrophizing, and avoidance was negatively associated with the rumination and helplessness components of significant other pain catastrophizing. Future research directions regarding the social context of pain are discussed.

Eccentric muscle contraction and stretching evoke mechanical hyperalgesia and modulate CGRP and P2X3 expression in a functionally relevant manner - Corrected Proof

2010-03-08

Abstract: Non-invasive, movement-based models were used to investigate muscle pain. In rats, the masseter muscle was rapidly stretched or electrically stimulated during forced lengthening to produce eccentric muscle contractions (EC). Both EC and stretching disrupted scattered myofibers and produced intramuscular plasma extravasation. Pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and vascular endothelial growth factor (VEGF) were elevated in the masseter 24h following EC. At 48h, neutrophils increased and ED1 macrophages infiltrated myofibers while ED2 macrophages were abundant at 4d. Mechanical hyperalgesia was evident in the ipsilateral head 4h–4d after a single bout of EC and for 7d following multiple bouts (1 bout/d for 4d). Calcitonin gene-related peptide (CGRP) mRNA increased in the trigeminal ganglion 24h following EC while immunoreactive CGRP decreased. By 2d, CGRP-muscle afferent numbers equaled naive numbers implying that CGRP is released following EC and replenished within 2d. EC elevated P2X3 mRNA and increased P2X3 muscle afferent neuron number for 12d while electrical stimulation without muscle contraction altered neither CGRP nor P2X3 mRNA levels. Muscle stretching produced hyperalgesia for 2d whereas contraction alone produced no hyperalgesia. Stretching increased CGRP mRNA at 24h but not CGRP-muscle afferent number at 2–12d. In contrast, stretching significantly increased the number of P2X3 muscle afferent neurons for 12d. The sustained, elevated P2X3 expression evoked by EC and stretching may enhance nociceptor responsiveness to ATP released during subsequent myofiber damage. Movement-based actions such as EC and muscle stretching produce unique tissue responses and modulate neuropeptide and nociceptive receptor expression in a manner particularly relevant to repeated muscle damage.

Catastrophizing and pain coping: Moving forward - Corrected Proof

Francis J. Keefe, Rebecca A. Shelby, Tamara J. Somers — 2010-03-08

The article by Campbell et al. in this issue provides a novel analysis of how catastrophizing can influence the effects of a pain coping strategy (i.e., distraction). The results are interesting in that they suggest, when exposed to pain, persons who are high catastrophizers are less likely to experience the immediate pain reducing effects of distraction.

Toward understanding acceptance and psychological flexibility in chronic pain - Corrected Proof

Lance M. McCracken — 2010-03-08

According to the former baseball player, manager, and “philosopher” Yogi Berra, “you’ve got to be very careful if you don’t know where you are going, because you might not get there.” The paper by Fish and colleagues in this issue is useful because its methods and research questions suggest where we might go in the development of psychological approaches to chronic pain: we could more fully harness information technologies, build efficiencies into our methods when possible, and adopt methods that are increasingly both theoretically based and contextually sensitive. And as much as these may be among the current directions for many researchers and clinicians, it can help to reaffirm these now and again.

A short goal-pursuit intervention to improve physical capacity: A randomized clinical trial in chronic back pain patients - Corrected Proof

Sandra Christiansen, Gabriele Oettingen, Bernhard Dahme, Regine Klinger — 2010-03-04

Abstract: The present study tested a short intervention using goal-pursuit strategies to increase physical capacity in pain patients. Sixty chronic back pain patients were randomly assigned to intervention or control conditions. Both groups followed a 3-week conventional back pain program at an outpatient back pain center. Instead of routine treatment, the intervention group received a one-hour intervention consisting of a combination of (a) a goal-setting strategy (i.e., mental contrasting, MC) aimed at commitment to improved physical capacity, (b) a short cognitive behavioral therapy-oriented problem-solving approach (CBT) to help patients overcome the obstacles associated with improving physical capacity, and (c) a goal-pursuit strategy, i.e., implementation intentions (II) aimed at performing physical exercise regularly. At two follow-ups (3weeks after discharge and 3months after returning home) the MCII-CBT group had increased its physical capacity significantly more than the control group as measured by both behavioral measures (ergometer, lifting) and subjective ratings. Findings are discussed with relation to the use of the intervention as a specific treatment to increase chronic pain patients’ motivation to be physically active.

Placebo and treatment group responses in postherpetic neuralgia vs. painful diabetic peripheral neuropathy clinical trials in the REPORT database - Corrected Proof

2010-03-04

Although several classes of medications are considered first-line treatments for neuropathic pain , many patients experience either intolerable adverse effects or pain that is partially or completely refractory to these treatments. These limitations have provided the impetus for the development of improved treatments. However, in an increasing number of randomized clinical trials (RCTs), the primary efficacy analyses have failed to show significant differences between the medication and placebo groups, despite previous preclinical and clinical studies suggesting that efficacy would be expected (e.g., ). Although these results have focused attention on the research methods used in chronic pain trials , it remains unclear whether they reflect a true lack of efficacy in the specific conditions studied or whether other unexplored factors have accounted for the lack of success in demonstrating efficacy.

Peripheral inflammation induces tumor necrosis factor dependent AMPA receptor trafficking and Akt phosphorylation in spinal cord in addition to pain behavior - Corrected Proof

2010-03-04

Abstract: In the present study, intraplantar carrageenan induced increased mechanical allodynia, phosphorylation of PKB/Akt and GluR1 ser 845 (PKA site) as well as GluR1, but not GluR2 movement into neuronal membranes. This change in membrane GluR1/GluR2 ratio is indicative of Ca2+ permeable AMPA receptor insertion. Pain behavior was reduced and biochemical changes blocked by spinal pretreatment, but not post-treatment, with a tumor necrosis factor (TNF) antagonist, Etanercept (100μg). Pain behavior was also reduced by spinal inhibition of phosphatidylinositol 3-kinase (PI-3K) (wortmannin; 1 and 5μg) and LY294002; 50 and 100μg) and Akt (Akt inhibitor IV; 3μg). Phosphorylated Akt was found exclusively in neurons in grey matter and in oligodendrocytes in white matter. Interestingly, this increase was seen first in superficial dorsal horn and α-motor neurons (peak 45min) and later (peak 2h post-injection) in deep dorsal horn neurons. Akt and GluR1 phosphorylation, AMPA receptor trafficking and mechanical allodynia were all TNF dependent. Whether phosphorylation of Akt and of GluR1 are in series or in parallel or upstream of pain behavior remains to be determined. Certainly, TNF-mediated GluR1 trafficking appears to play a major role in inflammatory pain and TNF-mediated effects such as these could represent a path by which glia contribute to neuronal sensitization (spinal LTP) and pathological pain.

PAIN’s new policy on spinal administration of non-approved drugs - Corrected Proof

Michael C. Rowbotham — 2010-03-04

In this issue of PAIN, Eisenach, Shafer, and Yaksh provide an important Commentary on publication of studies using spinal administration of non-approved drugs . The Commentary was inspired by the recent publication in PAIN of a small randomized controlled trial by Munts and colleagues of intrathecal glycine for dystonia associated with complex regional pain syndrome (CRPS) . No preclinical testing for neurotoxicity had been performed with the formulation to be administered. After use in a single patient was approved by the local Ethics Committee in the Netherlands, the authors then received Ethics Committee approval for a controlled clinical trial. The article did not state if government regulatory agency review was either required or obtained.

Cancer pain terminology: Time to develop a taxonomy that promotes good clinical practice and allows research to progress - Corrected Proof

Michael I. Bennett — 2010-03-02

The IASP Global Year on Cancer Pain that concluded in October 2009 focused attention on how well cancer pain is managed and highlighted the future research challenges. It has been over 20years since the publication of the WHO Method for Cancer Pain Relief put oral opioids on the clinical map and showed that the oral route is an effective intervention for around 75% of cancer patients . Yet even in developed countries cancer pain remains prevalent, is of moderate to severe intensity for many, and is undertreated for almost half of all patients . The emerging picture is sobering for clinical and research communities alike. While there is clearly a need for more basic science research into the understanding of cancer pain and its treatment, waiting for these new discoveries takes the spot-light away from a more uncomfortable reality: the need to address and improve our clinical practice.

Serine proteases and protease-activated receptor 2-dependent allodynia: A novel cancer pain pathway - Corrected Proof

D.K. Lam, B.L. Schmidt — 2010-03-02

Abstract: Mediators involved in the generation of pain in patients with cancer are poorly understood. Using a combined molecular, pharmacologic, behavioral, and genetic approach, we have identified a novel mechanism of cancer-dependent allodynia induced by protease-activated receptor 2 (PAR2). Here we show that human head and neck carcinoma cells have increased levels of proteolytic activity compared to normal human cell controls. Supernatant from human carcinoma cells, but not controls, caused marked and prolonged mechanical allodynia in mice, when administered into the hindpaw. This nociceptive effect was abolished by serine protease inhibition, diminished by mast cell depletion and absent in PAR2-deficient mice. In addition, non-contact co-culture of trigeminal ganglion neurons with human head and neck carcinoma cells increased the proportion of neurons that exhibited PAR2-immunoreactivity. Our results point to a direct role for serine proteases and their receptor in the pathogenesis of cancer pain. This previously unrecognized cancer pain pathway has important therapeutic implications wherein serine protease inhibitors and PAR2 antagonists may be useful for the treatment of cancer pain.

Catastrophizing delays the analgesic effect of distraction - Corrected Proof

2010-02-26

Abstract: Behavioral analgesic techniques such as distraction reduce pain in both clinical and experimental settings. Individuals differ in the magnitude of distraction-induced analgesia, and additional study is needed to identify the factors that influence the pain relieving effects of distraction. Catastrophizing, a set of negative emotional and cognitive processes, is widely recognized to be associated with increased reports of pain. We sought to evaluate the relationship between catastrophizing and distraction analgesia. Healthy participants completed three sessions in a randomized order. In one session (Pain Alone), pain was induced by topical application of a 10% capsaicin cream and simultaneous administration of a tonic heat stimulus. In another session (Pain+Distraction), identical capsaicin+heat application procedures were followed, but subjects played video games that required a high level of attention. During both sessions, verbal ratings of pain were obtained and participants rated their degree of catastrophizing. During the other session (Distraction Alone) subjects played the video games in the absence of any pain stimulus. Pain was rated significantly lower during the distraction session compared to the “Pain Alone” session. In addition, high catastrophizers rated pain significantly higher regardless of whether the subjects were distracted. Catastrophizing did not influence the overall degree of distraction analgesia; however, early in the session high catastrophizers had little distraction analgesia, though later in the session low and high catastrophizers rated pain similarly. These results suggest that both distraction and catastrophizing have substantial effects on experimental pain in normal subjects and these variables interact as a function of time.

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

2010-02-26

Abstract: 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 17years 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±2.6years) were enrolled. The VNS correlated with the VAS: ric=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 8–17years but is not interchangeable with the VAS.

Validation of the Chronic Pain Acceptance Questionnaire (CPAQ) in an Internet sample and development and preliminary validation of the CPAQ-8 - Corrected Proof

Rosemary A. Fish, Brian McGuire, Michael Hogan, Todd G. Morrison, Ian Stewart — 2010-02-26

Abstract: This study investigated the psychometric properties of the Chronic Pain Acceptance Questionnaire (CPAQ) in a mixed chronic pain, Internet sample and sought to develop a valid and reliable short form. Questionnaires were completed by 428 respondents, comprising a sample accessed via the Internet (n=319) and a sample who completed a paper and pencil version of the measures (n=109). Using confirmatory factor analysis (CFA) the two-factor structure of the CPAQ in the Internet sample was supported, though a good model fit was only achieved following the removal of one item. The resultant 19 item CPAQ demonstrated good reliability and evidence of validity was obtained for this sample. Data from the Internet sample were used to derive an eight-item short form. The two four-item factors (activity engagement [AE] and pain willingness [PW]) were confirmed using CFA and found to be invariant across both samples with good scale reliability. Higher CPAQ-8 and subscale scores were correlated with less depression and anxiety, pain severity and pain interference, and fewer medical visits for pain. Using structural equation modelling both subscales were found to partially mediate the impact of pain severity on pain interference and emotional distress. In this model AE had stronger associations with outcomes while PW accounted for a small portion of the variance in pain interference and anxiety, but not depression. This study confirmed the two-factor structure of the CPAQ in a mixed chronic pain Internet sample and provides preliminary evidence for the psychometric soundness of the CPAQ-8.

The role of motivation in distracting attention away from pain: An experimental study - Corrected Proof

2010-02-26

Abstract: Research on the effectiveness of distraction as a method of pain control is inconclusive. One mechanism pertains to the motivational relevance of distraction tasks. In this study the motivation to engage in a distraction task during pain was experimentally manipulated. Undergraduate students (N=73) participated in a cold pressor test (CPT) and were randomly assigned to three groups: a distraction-only group performed a tone-detection task during the CPT, a motivated-distraction group performed the same task and received a monetary reward for good task performance, and a control group did not perform the tone-detection task. Results indicated that engagement in the distraction task was better in the motivated-distraction group in comparison with the distraction-only group. Participants in both distraction groups experienced less pain compared to the control group. There were no overall differences in pain intensity between the two distraction groups. The effect of distraction was influenced by the level of catastrophic thinking about pain. For low catastrophizers, both distraction groups reported less pain as compared to the non-distracted control group. This was not the case for high catastrophizers. For high catastrophizers it mattered whether the distraction task was motivationally relevant: high catastrophizers reported less intense pain in the motivated-distraction group, as compared to the non-distracted control group. We conclude that increasing the motivational relevance of the distraction task may increase the effects of distraction, especially for those who catastrophize about pain.

Inclusion of authorized deception in the informed consent process does not affect the magnitude of the placebo effect for experimentally induced pain - Corrected Proof

Andrea L. Martin, Joel Katz — 2010-02-22

Abstract: The ethics of placebo research have been of paramount concern since the discovery of the phenomenon. To address these ethical concerns, Miller and colleagues (PLoS Med 2005 Sep;2(9):e262, 0853–0859) propose an alternate approach to placebo research, called “authorized deception”, in which participants are alerted of the use of deception in the research prior to study enrollment and thus knowingly permit its use if they decide to participate. The present study sought to investigate the authorized deception methodology in experimentally induced placebo analgesia. The participants were randomly assigned to an authorized deception or non-authorized deception group. A commonly used protocol was employed wherein heat pain stimulation was surreptitiously lowered following the application of a placebo cream during a series of conditioning trials and the magnitude of the placebo effect was subsequently assessed in test trials for which the stimulus intensity was the same for both the placebo and control creams. Authorized deception did not have any negative impact on the magnitude of the placebo effect, recruitment and retention of participants, nor did it result in any significant psychological harm. The majority of participants who received this form of consent preferred it to the traditional approach in which the participants are not alerted to the presence of deception. These findings suggest that the use of authorized deception is a viable and ethically preferable alternative consent process for laboratory-based studies on placebo analgesia. Further studies are needed to examine the effect of authorized deception in clinical trials and other placebo research within a clinical setting.

Cause or effect? Deconditioning and chronic low back pain - Corrected Proof

Jeanine A. Verbunt, Rob J. Smeets, Harriet M. Wittink — 2010-02-15

Physical inactivity is now universally accepted as the biggest public health problem of the 21st century in Western societies. Physical inactivity and the resulting physical deconditioning are associated with a host of chronic diseases of which non-specific chronic back pain (CLBP) may be one.

Clinical effectiveness: An approach to clinical trial design more relevant to clinical practice, acknowledging the importance of individual differences - Corrected Proof

2009-09-14

Schwartz and Lellouch distinguished between explanatory trials (examining whether an intervention works) and pragmatic trials (how best to use it in clinical practice). Clinical trials of new medicines are undertaken to satisfy the regulatory requirements that drugs be efficacious and safe on average. Regulatory trials are necessary, but not sufficient to answer many questions of practical importance. Are antidepressants better than anticonvulsants in neuropathic pain, and which antidepressant or anticonvulsant is best? Does failure to respond to one drug preclude response to another drug, both within and across classes? We do not yet know how to predict efficacy in individual patients. To guide treatment choice and care pathway development, determining what sequence of interventions produces worthwhile benefit in the largest number in the shortest time involves a different approach to clinically relevant outcomes.