The Journal of Pain

The Effects of Brief Mindfulness Meditation Training on Experimentally Induced Pain

Fadel Zeidan, Nakia S. Gordon, Junaid Merchant, Paula Goolkasian — 2009-10-23

Abstract: This study investigated the effects of brief mindfulness meditation training on ratings of painful electrical stimulation. In Experiment 1, we used a 3-day (20 min/d) mindfulness meditation intervention and measured pain ratings before and after the intervention. Participants' numerical ratings of pain to “low” and “high” electrical stimulation significantly decreased after meditation training. Pain sensitivity, measured by change in stimulus intensity thresholds, also decreased after training. We investigated, in Experiment 2, how well relaxation and a math distraction task attenuated experimental pain. Math distraction but not relaxation reduced high pain ratings. There was no reduction in pain sensitivity in these participants. In Experiment 3, we directly compared the effects of meditation with math distraction and relaxation conditions. Our findings indicated significant effects of both meditation and math distraction. Consistent with what was observed in Experiment 1, these participants also demonstrated a decrease in pain sensitivity after meditation training. Changes in the mindfulness and anxiety assessments suggest that meditation's analgesic effects are related to reduced anxiety and the enhanced ability to focus on the present moment.Perspective: Our findings indicate that a brief 3-day mindfulness meditation intervention was effective at reducing pain ratings and anxiety scores when compared with baseline testing and other cognitive manipulations. The brief meditation training was also effective at increasing mindfulness skills.

ASIC1 and ASIC3 Play Different Roles in the Development of Hyperalgesia After Inflammatory Muscle Injury

2009-12-16

Abstract: Acid-sensing ion channels (ASICs) respond to acidosis that normally occurs after inflammation. We examined the expression of ASIC1, ASIC2, and ASIC3 mRNAs in lumbar dorsal root ganglion neurons before and 24 hours after carrageenan-induced muscle inflammation. Muscle inflammation causes bilateral increases of ASIC2 and ASIC3 but not ASIC1 (neither ASIC1a nor ASIC1b) mRNA, suggesting differential regulation of ASIC1 versus ASIC2 and ASIC3 mRNA. Similar mRNA increases were observed after inflammation in knockout mice: ASIC2 mRNA increases in ASIC3-/- mice; ASIC2 and ASIC3 mRNAs increase in ASIC1-/- mice. Prior behavioral studies in ASIC3-/- mice showed deficits in secondary hyperalgesia (increased response to noxious stimuli outside the site of injury) but not primary hyperalgesia (increased response to noxious stimuli at the site of injury). In this study, we show that ASIC1-/- mice do not develop primary muscle hyperalgesia but develop secondary paw hyperalgesia. In contrast, and as expected, ASIC3-/- mice develop primary muscle hyperalgesia but do not develop secondary paw hyperalgesia. The pharmacological utility of the nonselective ASIC inhibitor A-317567, given locally, was tested. A-317567 reverses both the primary and the secondary hyperalgesia induced by carrageenan muscle inflammation. Thus, peripherally located ASIC1 and ASIC3 play different roles in the development of hyperalgesia after muscle inflammation.Perspective: This study shows changes in ASIC mRNA expression and behavioral hyperalgesia of C57Bl/6 (wild type), ASIC1-/-, and ASIC3-/- mice before and after the induction of muscle inflammation. A-317567 was effective in reversing hyperalgesia in these animals, suggesting the potential of ASICs as therapeutic targets for muscle inflammatory pain.

Depression Shows Divergent Effects on Evoked and Spontaneous Pain Behaviors in Rats

Miao Shi, Jin-Yan Wang, Fei Luo — 2010-01-22

Abstract: Although it has been accepted that depression and pain are common comorbidities, their interaction is not fully understood. The present study was aimed to investigate the effects of depression on both evoked pain behavior (thermal-induced nociception and hyperalgesia) and spontaneous pain behavior (formalin pain) in rats. An unpredictable chronic mild stress (UCMS) paradigm was employed to develop a classical depression. The emotional behaviors were assessed by sucrose preference test, open field test, and elevated plus-maze test. The results showed that the depressed rats always exhibited stronger tolerance to noxious thermal stimulation under both normal and complete Freund's adjuvant (CFA)-induced chronic pain conditions, when compared to nondepressed animals. Interestingly, the spontaneous nociceptive behaviors induced by formalin injection were significantly enhanced in rats exposed to UCMS in comparison to those without UCMS. Systemic administration of antidepressant fluoxetine significantly restored the nociceptive behaviors to normal level in depressed animals. An additional finding was that the inflammatory rats tended to display depressive-like behaviors without being exposed to UCMS. These results demonstrated that depression can have different effects on stimulus-evoked pain and spontaneous pain, with alleviation in the former while aggravation in the latter.Perspective: The present study provides evidence that depression can have divergent effects on stimulus-evoked and spontaneous pain by confirming that rats exposed to chronic mild stress tend to exhibit decreased pain sensitivity to experimental stimuli but increased intensity of ongoing pain. This may contribute to further understanding of the perplexing relationship between clinical depression and chronic pain.

A New Transient Sham TENS Device Allows for Investigator Blinding While Delivering a True Placebo Treatment

2009-11-30

Abstract: This study compared a new transient sham transcutaneous electrical nerve stimulation (TENS) that delivers current for 45 seconds to an inactive sham and active TENS to determine the degree of blinding and influence on pain reduction. Pressure-pain thresholds (PPT), heat-pain thresholds (HPT), and pain intensities to tonic heat and pressure were measured in 69 healthy adults before and after randomization. Allocation investigators and subjects were asked to identify the treatment administered. The transient sham blinded investigators 100% of the time and 40% of subjects compared to the inactive sham that blinded investigators 0% of the time and 21% of subjects. Investigators and subjects were blinded only 7% and 13% of the time, respectively, with active TENS. Neither placebo treatment resulted in significant changes in PPT, HPT, or pain intensities. Subjects using higher active TENS amplitudes (≥17 mAs) had significantly higher PPTs and lower pain intensities to tonic pressure than subjects using lower amplitudes (<17 mAs). HPTs and pain intensities to tonic heat were not significantly changed. The transient TENS completely blinds investigators to treatment and does not reduce pain, thereby providing a true placebo treatment.Perspective: This article presents the benefits of a new transient sham TENS device for use in prospective, randomized, clinical trials. This device facilitates blinding of subjects and investigators to eliminate expectation bias and determine the true efficacy of TENS for use in clinical populations.

Predictability of Painful Stimulation Modulates Subjective and Physiological Responses

2009-10-23

Abstract: Clinical observations suggest that the perceived intensity of a painful event increases as the unpredictability of its occurrence increases. We examined the effect of varying stimulus predictability on the Somatosensory Evoked Potential (SEP), Pupil Diameter Response (PDR), Pain Report (PR), and Fear Report (FR) in 25 healthy female volunteers experiencing repeated noxious fingertip shocks. Each volunteer underwent high- and low-stimulus intensities in 4 stimulus patterns defined by stimulus sequence (SEQ) and interstimulus interval (ISI) as follows: A) serial stimulus intensity SEQ with fixed ISI; B) serial stimulus intensity SEQ with varied ISI; C) random stimulus intensity SEQ with fixed ISI; and D) random stimulus intensity SEQ with varied ISI. Results revealed that: (1) lower stimulus predictability led to higher PR and FR, greater PDR magnitude, and greater SEP amplitude; and (2) the 4 dependent measures showed the same response pattern across levels of stimulus predictability. These findings support the hypothesis that lower stimulus predictability is associated with higher reported pain and fear as well as greater physiological arousal.Perspective: Patients undergoing painful procedures experience more distress when the occurrence of a painful event is unpredictable. Poor predictability increases pain, fear, and associated physiological arousal. Maximizing the predictability of painful events may improve the quality of patient care by minimizing associated levels of pain and fear.

Neonatal Bladder Inflammation Produces Functional Changes and Alters Neuropeptide Content in Bladders of Adult Female Rats

2009-11-30

Abstract: Neonatal bladder inflammation has been demonstrated to produce hypersensitivity to bladder re-inflammation as an adult. The purpose of this study was to investigate the effects of neonatal urinary bladder inflammation on adult bladder function and structure. Female Sprague-Dawley rats were treated on postnatal days 14 to 16 with intravesical zymosan or anesthesia alone. At 12 to 16 weeks of age, micturition frequency and cystometrograms were measured. Similarly treated rats had their bladders removed for measurement of plasma extravasation after intravesical mustard oil, for neuropeptide analysis (calcitonin gene-related peptide or Substance P) or for detailed histological examination. Rats treated with zymosan as neonates exhibited increased micturition frequency, reduced micturition volume thresholds, greater extravasation of Evans blue after intravesical mustard oil administration, and greater total bladder content of calcitonin gene-related peptide and Substance P. In contrast, there were no quantitative histological changes in the thickness, fibrosis, or mast cells of bladder tissue due to neonatal zymosan treatments. Functional changes in urologic systems observed in adulthood, coupled with the increased neuropeptide content and neurogenic plasma extravasation in adult bladders, suggest that the neonatal bladder inflammation treatment enhanced the number, function, and/or neurochemical content of primary afferent neurons. These data support the hypothesis that insults to the urologic system in infancy may contribute to the development of adult bladder hypersensitivity.Perspective: Inflammation of the bladder early in life in the rat has multiple sequelae, including laboratory measures that suggest an alteration of the neurophysiological substrates related to the bladder. Some painful bladder syndromes in humans have similar characteristics and so may be due to similar mechanisms.

Bilateral Mechanical-Pain Sensitivity Over the Trigeminal Region in Patients With Chronic Mechanical Neck Pain

2009-11-30

Abstract: The aim of this study was to investigate bilateral pressure-pain sensitivity over the trigeminal region, the cervical spine, and the tibialis anterior muscle in patients with mechanical chronic neck pain. Twenty-three patients with neck pain (56% women), aged 20 to 37 years old, and 23 matched controls (aged 20 to 38 years) were included. Pressure pain thresholds (PPTs) were bilaterally assessed over masseter, temporalis, and upper trapezius muscles, the C5-C6 zygapophyseal joint, and the tibialis anterior muscle in a blinded design. The results showed that PPT levels were significantly decreased bilaterally over the masseter, temporalis, and upper trapezius muscles, and also the C5-C6 zygapophyseal joint (P < .001), but not over the tibialis anterior muscle (P = .4) in patients with mechanical chronic neck pain when compared to controls. The magnitude of PPT decreases was greater in the cervical region as compared to the trigeminal region (P < .01). PPTs over the masseter muscles were negatively correlated to both duration of pain symptoms and neck-pain intensity (P < .001). Our findings revealed pressure-pain hyperalgesia in the trigeminal region in patients with mechanical chronic neck pain, suggesting spreading of sensitization to the trigeminal region in this patient population.Perspective: This article reveals the presence of bilateral pressure-pain hypersensitivity in the trigeminal region in patients with idiopathic neck pain, suggesting a sensitization process of the trigemino-cervical nucleus caudalis in this population. This finding has implications for development of management strategies.

Pharmacological Treatment of Neuropathic Facial Pain in the Dutch General Population

2009-12-17

Abstract: Few drugs are registered for treatment of neuropathic facial pain (NFP), and not much is known about treatment choices for NFP in daily practice. Patients with NFP were identified in the IPCI-database with longitudinal electronic general practitioner (GP) records. We described prescription patterns of pain medication following first symptoms. Off-label, off-guideline use, failure and reasons for failure were assessed. Failure was defined as treatment switch, exacerbation, adverse event, or invasive treatment for NFP. Of 203 NFP cases, 160 (79%) received pharmacological pain treatment. Most patients (90%) were initially treated by a GP with anti-epileptic drugs (55%) or NSAIDs (16%) as monotherapy. The median treatment delay was 0 days (range 0 to 2,478 days). Adverse events were experienced by 16 (10%) of patients. Sixty-two percent of first prescriptions were in adherence to guidelines and 59% were considered on-label while 34% of prescriptions were both off-label and off-guideline. Of the first therapy, 38% failed within 3 months. The median duration until failure was 251 days. General practitioners usually are the first to treat NFP. They usually prescribe drugs licensed for NFP and according to guidelines, but the extent of off-label use is substantial. Initial treatment often failed within a short period after starting therapy.Perspective: This drug-utilization study describes the pharmacological treatment of different forms of neuropathic facial pain in daily practice. Although treatment is mostly initiated rapidly by general practitioners in a correct way, it often contains off-label or off-guideline medication. Failure of the initial treatment is common and occurs rapidly as well.

The Assessment of Pain Quality: An Item Response Theory Analysis

2010-03-01

Abstract: Item Response Theory (IRT) is being increasingly used to develop and evaluate outcome measures. However, many pain measures, including those that assess pain quality, have yet to be evaluated from the IRT perspective. The current study evaluated the scales of a commonly used measure of pain quality (the Pain Quality Assessment Scale, or PQAS) using IRT analyses in 3 samples of patients with chronic pain. The findings indicated variability in the precision of the scales, suggesting that all 3 of the PQAS scales are precise when pain is severe and that the Paroxysmal and Deep scales but not necessarily the Surface scale are precise when pain is of moderate or lower severity. In addition, 2 potential problems with the 11 (ie, 0 to 10) response levels used for the PQAS items were identified: (1) a high degree of overlap between adjacent response levels and (2) a lack of interval scaling. Research is needed to determine the extent to which these problems do, or do not, threaten the validity of the PQAS items and scales as outcome measures in pain clinical trials.Perspective: IRT analyses provide important information about the psychometric and practical qualities of pain measures that is not provided by standard (classical test theory) analyses. IRT analyses of the PQAS subscales indicate that some of the scales are more precise than others at different levels of pain severity and provide important directions for further research to better understand the PQAS. IRT analyses would probably similarly provide important information concerning the utility of other measures commonly used in pain research.

Learned Avoidance From Noxious Mechanical Simulation But Not Threshold Semmes Weinstein Filament Stimulation After Nerve Injury in Rats

Hsiang-En Wu, Geza Gemes, Vasiliki Zoga, Takashi Kawano, Quinn H. Hogan — 2009-11-30

Abstract: Noxious mechanical stimulation evokes a complex and sustained hyperalgesic motor response after peripheral nerve injury that contrasts with a brief and simple withdrawal seen after noxious stimulation in control animals or after threshold punctate mechanical stimulation by the von Frey technique. To test which of these behaviors indicate pain, the aversiveness of the experience associated with each was determined using a passive avoidance test in rats after sciatic nerve ligation (SNL) or skin incision alone. After 18 days, step-down latency was measured during 9 sequential trials at 10-minute intervals. At each trial, rats received either no stimulus, needle stimuli, or threshold Semmes Weinstein (SW) filament stimuli after stepping down. Reactions were either a hyperalgesic response or a brief reflexive withdrawal. In SNL animals, needle stimulation produced substantial learned avoidance when animals showed hyperalgesic responses but produced minimal prolonged latency in SNL animals that showed only simple withdrawal responses. No learned avoidance developed using threshold SW testing in SNL animals. These findings show that needle stimulation is aversive in rats responding with hyperalgesic behavior. In contrast, SW stimulation, as well as needle stimulation that produced mere withdrawal, is minimally aversive.Perspective: The validity of measures of pain in animals is open to question. We demonstrated that needle stimulation is aversive in rats that respond with hyperalgesic-type behavior and is therefore a valid indicator of pain. Stimulation by SW is minimally aversive and is a problematic indicator of pain.

Increased Cold-Pain Thresholds in Major Depression

Christiane Schwier, Anna Kliem, Michael Karl Boettger, Karl-Jürgen Bär — 2009-11-30

Abstract: Most previous studies indicated that patients suffering from major depressive disorder (MDD) showed a decreased sensitivity for external or skin surface pain, eg, for heat or electrical stimuli, as compared to healthy controls. Here, we investigated cold-pain thresholds in 20 unmedicated patients suffering from MDD and 20 matched controls. We applied the ascending method of limits which has previously been used for heat-pain assessment in patients with depression. Similar to previous results for heat-pain thresholds we found a decreased sensitivity for cold pain in patients with MDD as indicated by increased cold-pain thresholds. This difference was significant on the right arm, whereas only a trend was obtained on the left arm, thus suggesting a certain degree of lateralization, similar to that seen in heat-pain perception in patients suffering from MDD or adjustment disorder. The study confirms our previous results of a lower sensitivity for externally induced pain in patients with MDD. Moreover, it adds weight to the assumption of a lateralized perception of thermal pain in depression.Perspective: This investigation provides further evidence for reduced pain perception of externally applied stimuli in major depression. Thus, central-nervous correlates for this altered pain perception in major depression are worth examining in future studies in order to gain more insight into mechanisms of pain perception on the one hand, and pathology of depression on the other.

Tonic Pain Abolishes Cortical Habituation of Visual Evoked Potentials in Healthy Subjects

2009-12-16

Abstract: We investigated changes in visual cortex excitability by analyzing visual evoked potential (VEP) habituation in healthy subjects during tonic pain evoked by the cold-pressor test (CPT). We tested VEP amplitude habituation (slope of the linear regression line for N1-P1 amplitude from the 1st to 6th block of 100 sweeps) in 19 healthy volunteers during 4 experimental conditions: baseline; no-pain (hand held in warm water, 25°C); pain (hand held in cold water, 2–4°C); and the after-effects of tonic pain. During baseline and no-pain sessions, VEPs habituated normally across the 6 consecutive blocks (mean slope –.28 and –.18%), whereas during pain and its after-effects they failed to decrease (0%, and –.11%). Tonic pain induced by the CPT abolishes normal VEP habituation and the lack of habituation persists after the CPT is stopped. Tonic pain probably abolishes VEP habituation by acting on brainstem neural structures which modulate thalamo-cortical activation thereby changing visual cortex excitability.Perspective: This study shows that tonic pain alters visual cortex excitability, a brain region unrelated to pain processing. These changes probably reflect defensive strategies against pain. Extending the study from healthy volunteers to patients with migraine between attacks would offer the opportunity to investigate visual cortical excitability under conditions when baseline habituation is absent.

Masthead

2010-03-01

Editorial Board

2010-03-01

The Journal of Pain

The Effects of Brief Mindfulness Meditation Training on Experimentally Induced Pain

ASIC1 and ASIC3 Play Different Roles in the Development of Hyperalgesia After Inflammatory Muscle Injury

Depression Shows Divergent Effects on Evoked and Spontaneous Pain Behaviors in Rats

A New Transient Sham TENS Device Allows for Investigator Blinding While Delivering a True Placebo Treatment

Predictability of Painful Stimulation Modulates Subjective and Physiological Responses

Neonatal Bladder Inflammation Produces Functional Changes and Alters Neuropeptide Content in Bladders of Adult Female Rats

Bilateral Mechanical-Pain Sensitivity Over the Trigeminal Region in Patients With Chronic Mechanical Neck Pain

Pharmacological Treatment of Neuropathic Facial Pain in the Dutch General Population

The Assessment of Pain Quality: An Item Response Theory Analysis

Learned Avoidance From Noxious Mechanical Simulation But Not Threshold Semmes Weinstein Filament Stimulation After Nerve Injury in Rats

Increased Cold-Pain Thresholds in Major Depression

Tonic Pain Abolishes Cortical Habituation of Visual Evoked Potentials in Healthy Subjects

Masthead

Editorial Board

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