Changes In Pain Sensitivity Research Articles

Beep Tones Attenuate Pain following Pavlovian Conditioning of an Endogenous Pain Control Mechanism

Heterotopic noxious counter-stimulation (HNCS) is commonly used to study endogenous pain control systems. The resulting pain inhibition is primarily based on spinal cord-brainstem loops. Recently, functional imaging studies have shown that limbic structures like the anterior cingulate cortex and amygdala are also implicated. Since these structures are involved in learning processes, it is possible that the HNCS-induced pain inhibition may depend on specific cues from the environment that have been associated with pain reduction through associative learning. We investigated the influence of Pavlovian conditioning on HNCS-induced pain inhibition in 32 healthy subjects by using a differential conditioning paradigm in which two different acoustic stimuli were either repeatedly paired or unpaired with HNCS. Series of noxious electrical pulse trains delivered to the non-dominant foot served as test stimuli. Diffuse noxious inhibitory control (DNIC)-like effects were induced by concurrent application of tonic HNCS (immersion of the contralateral hand in ice water). Subjective pain intensity and pain unpleasantness ratings and electromyographic recordings of the facial corrugator muscle and the nocifensive RIII flexion reflex were used to measure changes in pain sensitivity. HNCS induced significant pain and reflex inhibitions. In the post-conditioning phase, only the paired auditory cue was able to significantly reduce pain perceptions and corrugator muscle activity. No conditioned effect could be observed in RIII reflex responses. Our results indicate that the functional state of endogenous pain control systems may depend on associative learning processes that, like in the present study, may lead to an attenuation of pain perception. Similar albeit opposite conditioning of pain control mechanisms may significantly be involved in the exacerbation and chronification of pain states.

Reliability and validity of a simple and clinically applicable pain stimulus: sustained mechanical pressure with a spring-clamp

Generalized hyperalgesia, a widespread increased sensitivity to painful stimuli, has been demonstrated in a range of chronic pain conditions including low-back pain. The evidence suggests, that generalized hyperalgesia may be an important factor in the development of chronicity, but it is not commonly assessed in clinical practice. Whereas a range of tools and procedures for the quantitative sensory testing of pain sensitivity is available for laboratory pain research, most experimental pain stimuli are not well suited for clinical practice. In the current study, a simple and inexpensive mechanical spring-clamp was tested as a potential experimental pain stimulus. Ten seconds of mechanical pressure was applied to the thumb of 242 study participants: Healthy volunteers and low-back-pain patients (hospital and primary care). Pain intensity was measured by visual analogue scale before and after conditioned pain modulation by cold-pressor test (CPT). Correlation to pressure pain threshold (PPT) of the infraspinatus muscle and cold-pressor test pain intensity, time to pain onset and time to non-tolerance, was examined. Test/re-test reliability of clamp pain was also assessed and the stimulus–response relationship was examined with a set of 6 different clamps. Clamp pain was sensitive to changes in pain sensitivity provoked by conditioned pain modulation (CPM). Test/re-test reliability of the spring-clamp pain was better for healthy volunteers over a period of days, than for hospital patients over a period of weeks. A strong correlation (ρ = 0.73, P |003E; 0.0001) was found between clamp force and evoked pain intensity. Correlation to other pain stimuli varied, with a strong correlation between pre and post-CPM clamp pain intensity (ρ = 0.81, P > 0.0001), moderate correlation between clamp pain and PPT (ρ = −0.43, P > 0.0001), as well as CPT pain intensity (ρ = 0.32, P > 0.0001) and a weak correlation with time to onset of CPT pain (ρ = −0.14, P < 0.05). The application of mechanical pressure is commonly employed to assess general pain sensitivity, and a simple spring-clamp seems a potentially useful instrument for quantitative sensory testing in a clinical setting.

The association between changes in pressure pain sensitivity and changes in cardiovascular physiological factors associated with persistent stress

Objectives. To evaluate the possible association between pressure pain sensitivity of the chest bone (PPS) and cardiovascular physiological factors related to persistent stress in connection with a three-month PPS-guided stress-reducing experimental intervention programme. Methods. Forty-two office workers with an elevated PPS (≥ 60 arbitrary units) as a sign of increased level of persistent stress, completed a single-blinded cluster randomized controlled trial. The active treatment was a PPS (self-measurement)-guided stress management programme. Primary endpoints: Blood pressure (BP), heart rate (HR) and work of the heart measured as Pressure-Rate-Product (PRP); Secondary endpoints: Other features of the metabolic syndrome. Results. PPS decreased and changes in PPS after the intervention period were significantly associated with HR, PRP, body mass index (BMI) and visceral fat index (all correlation coefficients > 0.2, p < 0.05). Compared to the control cluster group, the active cluster group obtained a significant reduction in PPS, Low-density lipoprotein (LDL) cholesterol and total number of elevated risk factors (p < 0.05). On an individual level, significant and clinically relevant between-group reductions were observed in respect to BP, HR, PRP, total and LDL cholesterol, and total number of elevated risk factors (p < 0.05). Conclusions. The stress intervention method applied in this study induced a decrease in PPS which was associated with a clinically relevant decrease in resting blood pressure, heart rate, work of the heart and serum cholesterols.

Spinal Manipulative Therapy–Specific Changes in Pain Sensitivity in Individuals With Low Back Pain (NCT01168999)

Spinal manipulative therapy (SMT) is effective for some individuals experiencing low back pain; however, the mechanisms are not established regarding the role of placebo. SMT is associated with changes in pain sensitivity, suggesting related altered central nervous system response or processing of afferent nociceptive input. Placebo is also associated with changes in pain sensitivity, and the efficacy of SMT for changes in pain sensitivity beyond placebo has not been adequately considered. We randomly assigned 110 participants with low back pain to receive SMT, placebo SMT, placebo SMT with the instructional set “The manual therapy technique you will receive has been shown to significantly reduce low back pain in some people,” or no intervention. Participants receiving the SMT and placebo SMT received their assigned intervention 6 times over 2 weeks. Pain sensitivity was assessed prior to and immediately following the assigned intervention during the first session. Clinical outcomes were assessed at baseline and following 2 weeks of participation in the study. Immediate attenuation of suprathreshold heat response was greatest following SMT (P = .05, partial η2 = .07). Group-dependent differences were not observed for changes in pain intensity and disability at 2 weeks. Participant satisfaction was greatest following the enhanced placebo SMT. This study was registered at www.clinicaltrials.gov under the identifier NCT01168999. PerspectiveThe results of this study indicate attenuation of pain sensitivity is greater in response to SMT than the expectation of receiving an SMT. These findings suggest a potential mechanism of SMT related to lessening of central sensitization and may indicate a preclinical effect beyond the expectations of receiving SMT.

Effects of Deep Cervical Flexor Training on Pressure Pain Thresholds Over Myofascial Trigger Points in Patients With Chronic Neck Pain

ObjectiveThe purpose of this study was to assess the effects of a low-load training program for the deep cervical flexors (DCFs) on pain, disability, and pressure pain threshold (PPT) over cervical myofascial trigger points (MTrPs) in patients with chronic neck pain. MethodsThirty patients with chronic idiopathic neck pain participated in a 6-week program of specific training for the DCF, which consisted of active craniocervical flexion performed twice per day (10-20 minutes) for the duration of the trial. Perceived pain and disability (Neck Disability Index, 0-50) and PPT over MTrPs of the upper trapezius, levator scapulae, and splenius capitis muscles were measured at the beginning and end of the training period. ResultsAfter completion of training, there was a significant reduction in Neck Disability Index values (before, 18.2 ± 12.1; after, 13.5 ± 10.6; P < .01). However, no significant changes in PPT were observed over the MTrPs. ConclusionPatients performing DCF training for 6 weeks demonstrated reductions in pain and disability but did not show changes in pressure pain sensitivity over MTrPs in the splenius capitis, levator scapulae, or upper trapezius muscles.

Pressure algometry and thermal sensitivity for assessing pain sensitivity and effects of flunixin meglumine and sodium salicylate in a transient lameness model in sows

Sow lameness can result in decreased animal health and productivity, and is a significant animal welfare concern. Swine producers and veterinarians lack objective assessment tools to detect lameness. Objectives of this study were to evaluate pressure algometry (PA) and thermal sensitivity (TS) as objective assessment tools for changes in pain sensitivity associated with lameness and to assess analgesic drugs for mitigating lameness pain. Twelve mixed parity crossbred sows were anesthetized and injected with Amphotericin B in the distal interdigital space of both claws of one hind leg to induce transient lameness. Sows were randomly assigned to one of three analgesic treatment groups: (1) Sodium Salicylate (SS; 35mg/kg per os q.12h+0.04ml/kg IM q.24h sterile saline), (2) Flunixin meglumine (FM; 2.2mg/kg IM q.24h), or (3) Control (C; 0.04ml/kg IM q.24h sterile saline). All sows received each treatment over three trials with two-wk wash-out periods between trials. Forty-eight h post-induction, analgesic treatments were administered daily for four consecutive d. Pain sensitivity was assessed with PA and TS on each hind leg on d−1, d+1 and d+6 relative to induction (d0). Proc Glimmix of SAS 9.2 was used to analyze the difference between sound (S) and lame (L) legs on each trial day, with a simple effect comparison used to analyze effect of analgesia treatment on d+6. As predicted, S and L legs did not differ on d−1 (P=0.56) and less pressure was tolerated on L legs on d+1 (P<0.001) (Raw Means in kilograms of force: d−1 L 7.2±0.2; d−1 S 7.4±0.2; d+1 L 2.1±0.2; d+1 S 7.7±0.2kgf). A simple effect comparison of d+6 revealed no differences between FM and C (p=0.90), FM and SS (p=0.17), or SS and C (p=0.07). The TS latency of S versus L legs differed on all trial days (d−1 p=0.02, d+1 p<0.0001, d+6 p<0.01) over all trials. (TS Raw means (s): d−1 L 7.3±0.6; d−1 S 9.1±0.6; d+1 L 3.3±0.2; d+1 S 6.8±0.6; d+6 L 6.0±0.6; d+6 S 8.4±0.7s), including lame and sound days. In conclusion, these results support PA as an objective non-invasive method for measuring pain sensitivity in sows induced with transient lameness. Sodium salicylate or flunixin meglumine did not reduced pain sensitivity as measured by PA from d+1 to d+6 in this model of induced transient lameness.

Stress-Induced Allodynia – Evidence of Increased Pain Sensitivity in Healthy Humans and Patients with Chronic Pain after Experimentally Induced Psychosocial Stress

BackgroundExperimental stress has been shown to have analgesic as well as allodynic effect in animals. Despite the obvious negative influence of stress in clinical pain conditions, stress-induced alteration of pain sensitivity has not been tested in humans so far. Therefore, we tested changes of pain sensitivity using an experimental stressor in ten female healthy subjects and 13 female patients with fibromyalgia.MethodsMultiple sensory aspects of pain were evaluated in all participants with the help of the quantitative sensory testing protocol before (60 min) and after (10 and 90 min) inducing psychological stress with a standardized psychosocial stress test (“Trier Social Stress Test”).ResultsBoth healthy subjects and patients with fibromyalgia showed stress-induced enhancement of pain sensitivity in response to thermal stimuli. However, only patients showed increased sensitivity in response to pressure pain.ConclusionsOur results provide evidence for stress-induced allodynia/hyperalgesia in humans for the first time and suggest differential underlying mechanisms determining response to stressors in healthy subjects and patients suffering from chronic pain. Possible mechanisms of the interplay of stress and mediating factors (e.g. cytokines, cortisol) on pain sensitivity are mentioned. Future studies should help understand better how stress impacts on chronic pain conditions.

Normalization of Widespread Pressure Pain Hypersensitivity After Total Hip Replacement in Patients With Hip Osteoarthritis Is Associated With Clinical and Functional Improvements

To evaluate the relevance of ongoing nociceptive joint inputs to the maintenance of widespread pain hypersensitivity in patients with hip osteoarthritis (OA) and to determine whether a reversal in the widespread pressure hypersensitivity together with an improvement in pain and function occurs after total hip replacement in these patients. Forty patients with hip OA participated. Twenty patients underwent total hip replacement, and the other 20 patients were assigned to a waiting list. Pressure-pain thresholds (PPTs) over the second metacarpal bone and the gluteus medius, vastus medialis, vastus lateralis, and tibialis anterior muscles were assessed bilaterally with a pressure algometer before and 3 months after total hip replacement surgery. Assessments of pain intensity (by visual analog scale [VAS]), physical function (by the Western Ontario and McMaster Universities Osteoarthritis Index), and health status (by the Short Form 12 health survey and the EuroQol 5-domain index) were also performed. Patients who underwent total hip arthroplasty exhibited a reduction in widespread pressure pain hyperalgesia (increases in PPTs) over local and distant pain-free areas, as compared with before surgery and as compared with the patients assigned to the waiting list. PPTs were related to hip pain intensity, and significant correlations were found between higher VAS scores and lower average PPTs over all points assessed (-0.409 < r < -0.306, P < 0.05). Patients who underwent total hip arthroplasty exhibited a greater decrease in pain intensity and greater increases in function and health status than did those who were on the waiting list. Changes in the intensity of hip pain were moderately associated with changes in pressure pain sensitivity in the hip arthroplasty group. Normalization of widespread pressure pain hyperalgesia was found after successful hip joint replacement in patients with hip OA. Altered pain processing seems to be driven by ongoing peripheral joint pathology, which stresses the importance of reducing pain in OA.

Comparison of the Analgesic Effects of Dronabinol and Smoked Marijuana in Daily Marijuana Smokers

Recent studies have demonstrated the therapeutic potential of cannabinoids to treat pain, yet none have compared the analgesic effectiveness of smoked marijuana to orally administered Δ(9)-tetrahydrocannabinol (THC; dronabinol). This randomized, placebo-controlled, double-dummy, double-blind study compared the magnitude and duration of analgesic effects of smoked marijuana and dronabinol under well-controlled conditions using a validated experimental model of pain. Healthy male (N=15) and female (N=15) daily marijuana smokers participated in this outpatient study comparing the analgesic, subjective, and physiological effects of marijuana (0.00, 1.98, or 3.56% THC) to dronabinol (0, 10, or 20 mg). Pain response was assessed using the cold-pressor test (CPT): participants immersed their left hand in cold water (4 °C), and the time to report pain (pain sensitivity) and withdraw the hand from the water (pain tolerance) were recorded. Subjective pain and drug effect ratings were also measured as well as cardiovascular effects. Compared with placebo, marijuana and dronabinol decreased pain sensitivity (3.56%; 20 mg), increased pain tolerance (1.98%; 20 mg), and decreased subjective ratings of pain intensity (1.98, 3.56%; 20 mg). The magnitude of peak change in pain sensitivity and tolerance did not differ between marijuana and dronabinol, although dronabinol produced analgesia that was of a longer duration. Marijuana (1.98, 3.56%) and dronabinol (20 mg) also increased abuse-related subjective ratings relative to placebo; these ratings were greater with marijuana. These data indicate that under controlled conditions, marijuana and dronabinol decreased pain, with dronabinol producing longer-lasting decreases in pain sensitivity and lower ratings of abuse-related subjective effects than marijuana.

The effect of meloxicam on pain sensitivity, rumination time, and clinical signs in dairy cows with endotoxin-induced clinical mastitis

The objectives of this study were to (1) evaluate the use of a pressure algometer and an automated rumination monitoring system to assess changes in pain sensitivity and rumination time in response to endotoxin-induced clinical mastitis and (2) evaluate the effect of the nonsteroidal antiinflammatory drug meloxicam on pain sensitivity and rumination time, as well as other clinical signs, in dairy cattle with endotoxin-induced clinical mastitis. Clinical mastitis was induced in 12 primiparous and 12 multiparous lactating dairy cows by intramammary infusion of 25µg of Escherichia coli lipopolysaccharide (LPS) into 1 uninfected quarter. Immediately after, half the cows were injected subcutaneously with meloxicam (treated group) and half with the same volume of a placebo solution (control group). Pain sensitivity was assessed by measuring the difference in pressure required to elicit a response on the control and challenged quarter using an algometer 3 d before, immediately before, and at 3, 6, 12, and 24h after LPS infusion and either meloxicam or placebo injection. Rumination was continuously monitored from 2 d before to 3 d after LPS infusion using rumination loggers. Udder edema, body temperature, somatic cell score, and dry matter intake were also monitored to evaluate the occurrence and the duration of the inflammation after LPS infusion. In control animals, the difference in the pressure applied to the control and challenged quarters (control − challenged quarter) increased by 1.1±0.4kg of force 6h after LPS infusion compared with the baseline, suggesting an increase in pain sensitivity in the challenged quarter. Neither the LPS infusion nor the meloxicam treatment had an effect on daily rumination time. However, the rumination diurnal pattern on the day of LPS infusion showed an overall deviation from the baseline pattern. Cows spent less time ruminating in the hours following LPS infusion and more time ruminating later in the day. Meloxicam did not alter somatic cell score or dry matter intake. However, meloxicam-treated animals had less udder edema and a lower body temperature in the hours following LPS infusion compared with control animals. In conclusion, pressure algometers and rumination loggers show promise as tools to detect mastitis and monitor recovery on farm. Further, meloxicam has a beneficial effect in relieving pain and decreasing udder edema and body temperature in LPS-induced clinical mastitis.

Protein kinase C gamma (PKCγ) as a novel marker to assess the functional status of the corticospinal tract in experimental autoimmune encephalomyelitis (EAE)

In the spinal cord, PKCγ is an important kinase found in a specific subset of excitatory interneurons in the superficial dorsal horn and in axons of the corticospinal tract (CST). The major interest in spinal PKCγ has been its influences on regulating pain sensitivity but its presence in the CST also indicates that it has a significant role in locomotor function. A hallmark feature of the animal model commonly used to study Multiple Sclerosis, experimental autoimmune encephalolomyelitis (EAE) are motor impairments associated with the disease. More recently, it has also become recognized that EAE is associated with significant changes in pain sensitivity. Given its role in generating pain hypersensitivity and its presence in a major tract controlling motor activity, we set out to characterize whether EAE was associated with changes PKCγ levels in the spinal cord. We show here that EAE triggers a significant reduction in the levels of PKCγ, primarily in the CST. We did not observe any significant changes in PKCγ levels in the superficial dorsal horn but in general the levels tended to be below control levels in this region. In a final experiment we assessed the levels of PKCγ in the spinal cord of EAE mice that had recovered gross locomotor function and compared this to the levels found in EAE mice with chronic deficits. Our findings demonstrate that PKCγ levels are dynamic and that in later stages of the disease, its expression is dependent on the degree of motor function in the model. Taken together these results suggest that PKCγ may be a useful marker in the disease to monitor the status of the CST.

Effect of a single session of muscle-biased therapy on pain sensitivity: a systematic review and meta-analysis of randomized controlled trials.

BackgroundMuscle-biased therapies (MBT) are commonly used to treat pain, yet several reviews suggest evidence for the clinical effectiveness of these therapies is lacking. Inadequate treatment parameters have been suggested to account for inconsistent effects across studies. Pain sensitivity may serve as an intermediate physiologic endpoint helping to establish optimal MBT treatment parameters. The purpose of this review was to summarize the current literature investigating the short-term effect of a single dose of MBT on pain sensitivity in both healthy and clinical populations, with particular attention to specific MBT parameters of intensity and duration.MethodsA systematic search for articles meeting our prespecified criteria was conducted using Cumulative Index to Nursing and Allied Health Literature (CINAHL) and MEDLINE from the inception of each database until July 2012, in accordance with guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analysis. Relevant characteristics from studies included type, intensity, and duration of MBT and whether short-term changes in pain sensitivity and clinical pain were noted with MBT application. Study results were pooled using a random-effects model to estimate the overall effect size of a single dose of MBT on pain sensitivity as well as the effect of MBT, dependent on comparison group and population type.ResultsReports from 24 randomized controlled trials (23 articles) were included, representing 36 MBT treatment arms and 29 comparative groups, where 10 groups received active agents, 11 received sham/inert treatments, and eight received no treatment. MBT demonstrated a favorable and consistent ability to modulate pain sensitivity. Short-term modulation of pain sensitivity was associated with short-term beneficial effects on clinical pain. Intensity of MBT, but not duration, was linked with change in pain sensitivity. A meta-analysis was conducted on 17 studies that assessed the effect of MBT on pressure pain thresholds. The results suggest that MBT had a favorable effect on pressure pain thresholds when compared with no-treatment and sham/inert groups, and effects comparable with those of other active treatments.ConclusionThe evidence supports the use of pain sensitivity measures by future research to help elucidate optimal therapeutic parameters for MBT as an intermediate physiologic marker.

Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats

The serotonergic system plays an important role in cognitive functions via various 5-HT receptors. Vortioxetine (Lu AA21004) in development as a novel multimodal antidepressant is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (5-HTT) inhibitor in vitro. Preclinical studies suggest that 5-HT3 and 5-HT7 receptor antagonism as well as 5-HT1A receptor agonism may have a positive impact on cognitive functions including memory. Thus vortioxetine may potentially enhance memory. We investigated preclinical effects of vortioxetine (1–10mg/kg administered subcutaneously [s.c.]) on memory in behavioral tests, and on cortical neurotransmitter levels considered important in rat memory function. Contextual fear conditioning and novel object recognition tests were applied to assess memory in rats. Microdialysis studies were conducted to measure extracellular neurotransmitter levels in the rat medial prefrontal cortex. Vortioxetine administered 1h before or immediately after acquisition of contextual fear conditioning led to an increase in freezing time during the retention test. This mnemonic effect was not related to changes in pain sensitivity as measured in the hotplate test. Rats treated with vortioxetine 1h before training spent more time exploring the novel object in the novel object recognition test. In microdialysis studies of the rat medial prefrontal cortex, vortioxetine increased extracellular levels of acetylcholine and histamine. In conclusion, vortioxetine enhanced contextual and episodic memory in rat behavioral models. Further demonstration of its potential effect on memory functions in clinical settings is warranted.

Resident glial cell activation in response to perispinal inflammation leads to acute changes in nociceptive sensitivity: Implications for the generation of neuropathic pain

Injury or disease affecting the spinal cord is often accompanied by abnormal, chronic pain. Recent estimates suggest that approximately 60% of patients with multiple sclerosis are affected by significant changes in pain sensitivity or experience ongoing neuropathic pain of unknown etiology. Chronic pain is also a significant concern after direct spinal cord trauma. Inflammatory events and the changes in astrocyte and microglia reactivity at the spinal level in response to injury or disease are now recognized as important processes that can initiate pain hypersensitivity. Changes in the structural integrity or permeability of the blood–brain barrier/blood–spinal cord barrier (BBB/BSCB) can facilitate the inflammatory events that result in these abnormal pain states. It remains unclear, however, whether chronic pain in these disorders is dependent on the influx of peripheral leukocytes or whether changes in the reactivity of resident glial cells within the central nervous system alone are sufficient. To address this question, we generated a model of perispinal inflammation that resulted in significant changes in the reactivity of resident astrocytes and microglia within the spinal cord but maintained the integrity of the BSCB. A number of similar changes at the behavioural and cellular level occur in this model that mimic the responses seen in animal models of multiple sclerosis or spinal cord injury (SCI). However, these changes are short lived and resolve over the course of a 2-week observation period. Our findings suggest that the chronicity of pain after injury or disease in the nervous system is dependent on the integrity of the BBB/BSCB.

Pain sensitivity changes in chronic pain patients with and without spinal cord stimulation assessed by nociceptive withdrawal reflex thresholds and electrical pain thresholds

Abstract Background and aim Previous studies have shown that patients with chronic pain had significantly lower nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) than healthy controls. Patients with chronic pain and implanted spinal cord stimulator (SCS) system presents an opportunity to study dynamic pain sensitivity changes in a situation where patients just have been stimulated (i.e., pain-free or greatly reduced pain) and compare with the situation where patients are not stimulated (i.e., experiencing severe pain). Methods Seventeen volunteers with chronic neuropathic pain and a SCS implanted for pain relief participated in the experiment. Volunteers were asked to turn off the SCS and refrain from medication at least 8 h before the experiment. Electrical stimulation (train-of-five 1-ms pulses delivered at 200 Hz) was applied to the arc of the foot in order to elicit the NWR and electromyographic responses were recorded from tibialis anterior muscle. A staircase procedure was used to assess the NWR-T and a Visual-Analog-Scale (VAS) scale (range 0–10) was used to assess the EP-T. After the initial testing, the SCS was turned on, and thresholds were reassessed after 1 h. Paired t-tests were used to compare the thresholds before and after the SCS was turned on. All values are presented as mean ± SD. Results The NWR-T were significantly higher after the SCS was turned on (before: 16.3 ±8.1 mA; after: 19.0 ± 10.9 mA; p = 0.028). EP-T did not show any significant differences (before: 3.2 ± 1.5 mA; after: 2.9 ± 2.0 mA; p = 0.324). Conclusion Results showed a higher NWR-T after the SCS was turned on, which indicates a depression of spinal nociception. Moreover, the NWR-T was able to detect ongoing and relatively quick changes in pain sensitivity.

Validation of a porcine behavioural model of UVB induced inflammatory pain

Abstract Background and aim Cutaneous inflammation induced by ultraviolet B-light (UV-B) is considered a valuable translational pain model. Until now, the development of primary hyperalgesia has been assessed predominantly in rodents, whereas porcine skin might be advantageous due to its greater homology with human skin. The aim of the present study was to investigate porcine behavioural responses to nociceptive mechanical and thermal stimulations following UV-B inflammation. Methods One skin area of 4 cm2 in the flank of 16 male pigs of 55 ± 6 kg was irradiated by UV-B using 3xMED (Minimum Erythema Dose). Changes in pain sensitivity were assessed 24 and 48 h following irradiation via delivery of mechanical (Pressure Application Measurement device) and thermal (CO2 laser) stimulations to the inflamed skin area and to an untreated control site. Results All animals showed higher sensitivity in the inflamed skin site 24 and 48 h following irradiation, compared to the control site (P&lt; 0.05). Pressure withdrawal threshold decreased in the inflamed site: 231 g (148–451) against 408g (347–684) after 24 hours and 200 g (106–293) against 656g (405–902) after 48 h. Similarly, latency to respond to the laser stimulus was lower at the inflamed site: 5 s (3–7) against 9 s (4–2) after 24h and 4 s (3–15) against 20 s (8–25) after 48 h. One and two days after irradiation, a tendency was found for an increased cutaneous mechanical pain sensitivity compared to baseline values in the site irradiated with UV-B light (P = 0.092). Thermal sensitivity was increased within the inflamed site 24 h after irradiation with latency changing from 17s (4–25) at baseline to 5 s (3–7) at 24 h (P =0.001). At 48 h, the response latency had not decreased any further (P = 0.414). Conclusions Our study shows that behavioural recordings are a valid tool for the assessment of mechanical and heat sensitization following UV-B inflammation in porcine skin.

Immediate Changes in Widespread Pressure Pain Sensitivity, Neck Pain, and Cervical Range of Motion After Cervical or Thoracic Thrust Manipulation in Patients With Bilateral Chronic Mechanical Neck Pain: A Randomized Clinical Trial

Randomized clinical trial. To compare the effects of cervical versus thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain on pressure pain sensitivity, neck pain, and cervical range of motion (CROM). Evidence suggests that spinal interventions can stimulate descending inhibitory pain pathways. To our knowledge, no study has investigated the neurophysiological effects of thoracic thrust manipulation in individuals with bilateral chronic mechanical neck pain, including widespread changes on pressure sensitivity. Ninety patients (51% female) were randomly assigned to 1 of 3 groups: cervical thrust manipulation on the right, cervical thrust manipulation on the left, or thoracic thrust manipulation. Pressure pain thresholds (PPTs) over the C5-6 zygapophyseal joint, lateral epicondyle, and tibialis anterior muscle, neck pain (11-point numeric pain rating scale), and cervical spine range of motion (CROM) were collected at baseline and 10 minutes after the intervention by an assessor blinded to the treatment allocation of the patients. Mixed-model analyses of covariance were used to examine the effects of the treatment on each outcome variable, with group as the between-subjects variable, time and side as the within-subject variables, and gender as the covariate. The primary analysis was the group-by-time interaction. No significant interactions were found with the mixed-model analyses of covariance for PPT level (C5-6, P>.210; lateral epicondyle, P>.186; tibialis anterior muscle, P>.268), neck pain intensity (P = .923), or CROM (flexion, P = .700; extension, P = .387; lateral flexion, P>.672; rotation, P>.192) as dependent variables. All groups exhibited similar changes in PPT, neck pain, and CROM (all, P<.001). Gender did not influence the main effects or the interaction effects in the analyses of the outcomes (P>.10). The results of the current randomized clinical trial suggest that cervical and thoracic thrust manipulation induce similar changes in PPT, neck pain intensity, and CROM in individuals with bilateral chronic mechanical neck pain. However, changes in PPT and CROM were small and did not surpass their respective minimal detectable change values. Further, because we did not include a control group, we cannot rule out a placebo effect of the thrust interventions on the outcomes. Therapy, level 1b.J Orthop Sports Phys Ther 2012;42(9):806-814, Epub 18 June 2012. doi:10.2519/jospt.2012.4151.

Sensory Mapping of the Upper Trapezius Muscle in Relation to Consecutive Sessions of Eccentric Exercise

The aim of this study was to evaluate the changes in pressure pain sensitivity maps in untrained subjects over 2 subsequent sessions of eccentric exercise (ECC) expected to result in (a) delayed onset muscle soreness (DOMS) and (b) adaptation/recovery, respectively. Eleven healthy male subjects participated in this study. Pressure pain threshold (PPT), rate of perceived exertion (RPE), pain intensity, soreness area drawing, maximal voluntary contraction (MVC), and shoulder range of motion were assessed in session 1 before, immediately after, and 24 hours after ECC. The ECC protocol that was used to induce DOMS consisted of 50 eccentric contractions of the right shoulder that were divided into 5 bouts, including 10 contractions at MVC level separated by a 2-minute resting period. Session 2 was identical to session 1 and performed exactly 1 week later. There was only a significant increase in the RPE assessed before the exercise and 24 hours after the exercise in session 1 (p = 0.001). The average PPT only decreased significantly from before the exercise (660.2 ± 76.2 kPa) to 24 hours after the exercise (435.6 ± 59.3 kPa) in session 1 (p = 0.016). The present study confirmed a heterogeneous distribution of mechanical sensitivity before and after sessions of ECC. The first session of ECC underlined increased mechanical sensitivity because of DOMS, whereas the second session reflected an adaptation process. Our results support the potential role of ECC bouts in training regimens.

The Effects of Age on Pain Sensitivity: Preclinical Studies

Preclinical studies of pain and aging represent an area of research where considerations of age, strain, gender, and method of behavioral assessment are but some of the challenges that must be addressed. The results of studies related to the impact of age on pain sensitivity have ranged from increased to decreased sensitivity to no change. Examining the design of these studies one discovers that cross-sectional designs using animals of different ages have been used to evaluate age-related effects in normal animals as well as animals with inflammatory and neuropathic pain conditions. In the present review a summary of these studies is presented along with a discussion of potential mechanisms responsible for changes that have been described. The dominant method of behavioral assessment in the majority of studies involving rodents has been reflex-based strategies that unfortunately do not reveal the same effects of experimental manipulations known to affect pain sensitivity in humans. A comparison of results obtained with reflex-based methods versus those obtained with cortically dependent operant methods reveals significant differences. Increases in pain sensitivity under different experimental conditions have been suggested to result from age-related anatomical, physiological, and biochemical changes as well as compensatory changes in homeostatic mechanisms and intrinsic plasticity of somatosensory pathways involved in the processing and perception of pain. Other factors that may contribute to the impact of age on pain sensitivity include dysregulation of the hypothalamic-pituitary-adrenal axis and changes in autonomic function that occur with advancing age. In the future translational research in the field of pain and aging will need to focus on establishing clinically relevant animal models and assessment strategies to evaluate the causal relationships between the biological changes associated with advancing age and the varied behavioral changes in pain sensitivity.

Changes in pain sensitivity following spinal manipulation: A systematic review and meta-analysis

Spinal manipulation (SMT) is commonly used for treating individuals experiencing musculoskeletal pain. The mechanisms of SMT remain unclear; however, pain sensitivity testing may provide insight into these mechanisms. The purpose of this systematic review is to examine the literature on the hypoalgesic effects of SMT on pain sensitivity measures and to quantify these effects using meta-analysis. We performed a systematic search of articles using CINAHL, MEDLINE, PsycINFO, and SPORTDiscus from each databases’ inception until May 2011. We examined methodological quality of each study and generated pooled effect size estimates using meta-analysis software. Of 997 articles identified, 20 met inclusion criteria for this review. Pain sensitivity testing used in these studies included chemical, electrical, mechanical, and thermal stimuli applied to various anatomical locations. Meta-analysis was appropriate for studies examining the immediate effect of SMT on mechanical pressure pain threshold (PPT). SMT demonstrated a favorable effect over other interventions on increasing PPT. Subgroup analysis showed a significant effect of SMT on increasing PPT at the remote sites of stimulus application supporting a potential central nervous system mechanism. Future studies of SMT related hypoalgesia should include multiple experimental stimuli and test at multiple anatomical sites.