Healthy Pain-Free Individuals with a History of Distal Radius Fracture Demonstrate an Expanded Distribution of Experimental Referred Pain Toward the Wrist.

OBJECTIVE: Nociception caused by injuries may sensitize central mechanisms causing expanded pain areas. After recovery, the status of such pain distribution and sensitivity mechanisms is unknown. The present study investigated whether individuals who have fully recovered from a distal radius fracture demonstrate increased pain sensitivity and expanded distribution of pressure-induced pain. DESIGN: Cross-sectional single-blinded study. SETTING: Clinical setting. SUBJECTS: Twenty-three pain-free individuals with a history of painful distal radius fracture and 22 nonfractured, age/gender-matched controls participated in two experimental sessions (day 0, day 1) 24 hours apart. METHODS: Pressure pain thresholds (PPTs) were recorded bilaterally at the extensor carpi radialis longus (ECRL), infraspinatus, and gastrocnemius muscles. Spatial distribution of pain was assessed following 60-second painful pressure stimulation at the ECRL (bilateral) and the infraspinatus muscles on the fractured or dominant side. Participants drew pain areas on a body map. After day 0 assessments, prolonged pain was induced by eccentric exercise of wrist extensors on the fractured/dominant side. RESULTS: Compared with controls, pressure-induced ECRL pain in the fracture group referred more frequently toward the distal forearm (P < 0.005) on day 0. Both groups showed larger pain areas on day 1 compared with day 0 (P < 0.005), although the fracture group showed a larger relative change between days (P < 0.005). The fracture group showed larger pain areas on the fracture side compared with the contralateral side on both days (P < 0.005). CONCLUSIONS: Prolonged pain and recovered prior painful injuries like fractures may sensitize pain mechanisms manifested as expanded pain distribution. Pressure-induced referred pain can be a simple pain biomarker for clinical use.

Digital Pain Mapping and Tracking in Patients With Chronic Pain: Longitudinal Study.

BACKGROUND: Digital pain mapping allows for remote and ecological momentary assessment in patients over multiple time points spanning days to months. Frequent ecological assessments may reveal tendencies and fluctuations more clearly and provide insights into the trajectory of a patient's pain. OBJECTIVE: The primary aim of this study is to remotely map and track the intensity and distribution of pain and discomfort (eg, burning, aching, and tingling) in patients with nonmalignant spinal referred pain over 12 weeks using a web-based app for digital pain mapping. The secondary aim is to explore the barriers of use by determining the differences in clinical and user characteristics between patients with good (regular users) and poor (nonregular users) reporting compliance. METHODS: Patients (N=91; n=53 women) with spinal referred pain were recruited using web-based and traditional in-house strategies. Patients were asked to submit weekly digital pain reports for 12 weeks. Each pain report consisted of digital pain drawings on a pseudo-three-dimensional body chart and pain intensity ratings. The pain drawings captured the distribution of pain and discomfort (pain quality descriptors) expressed as the total extent and location. Differences in weekly pain reports were explored using the total extent (pixels), current and usual pain intensity ratings, frequency of quality descriptor selection, and Jaccard similarity index. Validated e-questionnaires were completed at baseline to determine the patients' characteristics (adapted Danish National Spine Register), disability (Oswestry Disability Index and Neck Disability Index), and pain catastrophizing (Pain Catastrophizing Scale) profiles. Barriers of use were assessed at 6 weeks using a health care-related usability and acceptance e-questionnaire and a self-developed technology-specific e-questionnaire to assess the accessibility and ease of access of the pain mapping app. Associations between total extent, pain intensity, disability, and catastrophizing were explored to further understand pain. Differences between regular and nonregular users were assessed to understand the pain mapping app reporting compliance. RESULTS: Fluctuations were identified in pain reports for total extent and pain intensity ratings (P<.001). However, quality descriptor selection (P=.99) and pain drawing (P=.49), compared using the Jaccard index, were similar over time. Interestingly, current pain intensity was greater than usual pain intensity (P<.001), suggesting that the timing of pain reporting coincided with a more intense pain experience than usual. Usability and acceptance were similar between regular and nonregular users. Regular users were younger (P<.001) and reported a larger total extent of pain than nonregular users (P<.001). CONCLUSIONS: This is the first study to examine digital reports of pain intensity and distribution in patients with nonmalignant spinal referred pain remotely for a sustained period and barriers of use and compliance using a digital pain mapping app. Differences in age, pain distribution, and current pain intensity may influence reporting behavior and compliance.

Corticomotor excitability reduction induced by experimental pain remains unaffected by performing a working memory task as compared to staying at rest.

Experimental pain inhibits primary motor cortex (M1) excitability. Attenuating pain-related inhibition of M1 excitability may be useful during rehabilitation in individuals with pain. One strategy to attenuate M1 excitability is to influence prefrontal and premotor cortex activity. Working memory tasks, e.g. the two-back task (TBT), engage prefrontal and premotor cortices and may influence M1 excitability. We hypothesized that performing the TBT during pain would influence pain-related changes in M1 excitability. Participants (n = 28) received rigorous training in the TBT before baseline testing. Experimental pain was induced by injecting hypertonic saline into the first dorsal interosseous (FDI) muscle. Participants rated pain intensity on a 0-10 numerical rating scale (NRS) every second min until pain-resolved (PR) during the performance of the TBT (n = 14) or during REST (n = 14). In the TBT, letters were presented pseudo-randomly, and accuracy and reaction time to identified letters corresponding to letters shown two times back were recorded. M1 excitability was assessed using transcranial magnetic stimulation. Motor-evoked potentials (MEPs) were recorded at baseline, and at PR, PR + 10, PR + 20, and PR + 30 min. Four minutes after hypertonic saline injection, the pain NRS scores were higher in the TBT group than the REST group (p = 0.009). No time × group interaction was found for MEPs (p = 0.73), but a main effect of time (p < 0.0005) revealed a reduction of MEPs at PR up until PR + 30 (p < 0.008). The TBT accuracy improved at PR + 30 in both groups (p = 0.019). In conclusion, the pain-induced reduction in corticomotor excitability was unaffected by performing a working memory task, despite greater pain in the TBT group.

Differential Corticomotor Excitability Responses to Hypertonic Saline-Induced Muscle Pain in Forearm and Hand Muscles.

Experimental muscle pain inhibits corticomotor excitability (CE) of upper limb muscles. It is unknown if this inhibition affects overlapping muscle representations within the primary motor cortex to the same degree. This study explored CE changes of the first dorsal interosseus (FDI) and extensor carpi radialis (ECR) muscles in response to muscle pain. Participants (n = 13) attended two sessions (≥48 hours in-between). Hypertonic saline was injected in the ECR (session one) or the FDI (session two) muscle. CE, assessed by transcranial magnetic stimulation (TMS) motor-evoked potentials (MEPs), was recorded at baseline, during pain, and twenty minutes postinjection together with pain intensity ratings. Pain intensity ratings did not differ between the two pain sites (p = 0.19). In response to FDI muscle pain, the MEPs of the FDI muscle were reduced at 2 and 4 min postinjection (p ≤ 0.03), but not after ECR muscle pain. No significant MEP change was detected for the ECR muscle (p = 0.62). No associations between MEPs and pain intensity were found (p > 0.2). The present results indicate that the output from overlapping cortical representations of two muscles differentially adapts to acute muscle pain.

A Test-Retest Reliability Study of Human Experimental Models of Histaminergic and Non-histaminergic Itch.

Numerous exploratory, proof-of-concept and interventional studies have used histaminergic and non-histaminergic human models of itch. However, no reliability studies for such surrogate models have been conducted. This study investigated the test-retest reliability for the response to histamine- and cowhage- (5, 15, 25 spiculae) induced itch in healthy volunteers. Cowhage spiculae were individually applied with tweezers and 1% histamine was applied with a skin prick test (SPT) lancet, both on the volar forearm. The intensity of itch was recorded on a visual analogue scale and self-reported area of itch was assessed 5 and 10 min after itch provocation. Reliability of the evoked itch (area under the curve and peak intensity) was assessed by the coefficient of variation (CV), intra-class correlation coefficient (ICC), and sample size estimation for parallel and cross-over designs. Cowhage (ICC = 0.57-0.77, CVbetween = 97%, CVwithin = 41%) and histamine: (ICC = 0.83-0.93, CVbetween = 97%, CVwithin = 20%) exhibited moderate-to-excellent intra-individual reliability and moderate inter-individual reliability for the itch intensity. For a test-retest observation period of one week, SPT-delivered histamine and application of cowhage-spiculae are reproducible human models of itch. The high inter-individual and low intra-individual variability suggests cross-over designed studies when applicable.

Psychophysical and Vasomotor Responses of the Oral Tissues: A Nicotine Dose-Response and Menthol Interaction Study.

INTRODUCTION: This study implemented an intra-oral test-platform to assess the sensory, psychophysical, and vasomotor responses to nicotine and menthol, alone or in combination. METHODS: Two double-blinded, placebo-controlled, randomized, cross-over studies, including healthy nonsmoking participants were performed. Study I: A dose-response relationship (N = 20) between 0, 2, and 4 mg nicotine gum. Study II: An interaction response (N = 22) to 30 mg menthol and 4 mg nicotine alone or in combination. Heart rate, blood pressure, tactile and thermosensory thresholds, intra-oral blood flow and temperature, pain/irritation intensities/locations, McGill Pain Questionnaire, and taste experience were assessed before, during or after the completion of a standardized chewing regime. RESULTS: A dose-response elevation in heart rate was attenuated when nicotine was combined with menthol. Blood flow, temperature, and warm-detection thresholds, as assessed on the tongue, similarly increased for all gums. Pain intensity and taste experiences were similar between nicotine doses. Nicotine attenuated the sweet, cooling, and freshening sensation of menthol. Within the first 4 minutes, menthol reduced the intensity but not the area of nicotine-induced pain and irritation. The 4-mg nicotine dose led to a continued increase in the intensity and area of irritation in the throat post-chewing. Moreover, one-half of participants responded to menthol as an irritant, and these individuals demonstrated larger areas of nicotine-induced irritation in the throat post-chewing. CONCLUSIONS: The intra-oral test platform provides a basis to optimize the assessment of nicotine-related taste and sensory experiences and can be used in future studies for profiling nicotine gum.

Interaction between intra-oral cinnamaldehyde and nicotine assessed by psychophysical and physiological responses.

Cinnamaldehyde and nicotine activate the transient receptor potential subtype A1 (TRPA1) channel, which may cause burning sensations. This study investigated whether cinnamaldehyde modulates nicotine-induced psychophysical and physiological responses in oral tissues. Healthy non-smokers (n = 22) received, in a randomized, double-blind, crossover design, three different gums containing 4 mg of nicotine, 20 mg of cinnamaldehyde, or a combination thereof. Assessments of orofacial temperature and blood flow, blood pressure, heart rate, taste experience, and intra-oral pain/irritation area and intensity were performed before, during, and after a 10-min chewing regime. Cinnamaldehyde increased the temperature of the tongue and blood flow of the lip, and was associated with pain/irritation, especially in the mouth. Nicotine increased the temperature of the tongue and blood flow of the cheek, and produced pain/irritation in the mouth and throat. The combination of cinnamaldehyde and nicotine did not overtly change the psychophysical or physiological responses. Interestingly, half of the subjects responded to cinnamaldehyde as an irritant, and these cinnamaldehyde responders reported greater nicotine-induced pain/irritation areas in the throat. Whether sensitivity to cinnamaldehyde can predict the response to nicotine-induced oral irritation remains to be determined. A better understanding of the sensory properties of nicotine in the oral mucosa has important therapeutic implications because pain and irritation represent compliance issues for nicotine replacement products.

Chronic neck pain alters muscle activation patterns to sudden movements.

The aim of this study was to assess the activation of the sternocleidomastoid (SCM) and splenius capitis (SC) muscles in response to unanticipated, full body perturbations in individuals with chronic neck pain (NP) and age-matched healthy controls (HC). Individuals with NP had a history of NP for 8.9 ± 7.8 years, rated the intensity of NP as 4.2 ± 2.0 (score out of 10), and scored 15.3 ± 6.5 on the Neck Disability Index. Participants stood on a moveable platform during which 32 randomized postural perturbations (eight repetitions of four perturbation types: 8 cm forward slide (FS), 8 cm backward slides, 10° forward tilt, and 10° backward tilt) with varying inter-perturbation time intervals were performed over a period of 5 min. Bilateral surface electromyography (EMG) from the SCM and SC was recorded, and the onset time and the average rectified value of the EMG signal was determined for epochs of 100 ms; starting 100 ms prior to and 500 ms after the perturbation onset. Individuals with NP, as compared to HC, demonstrated delayed onset times and reduced EMG amplitude of the SCM and SC muscles in response to all postural perturbations. Such findings were most pronounced following the FS postural perturbation (healthy vs. NP for SCM 83.3 ± 8.0 vs. 86.3 ± 4.4 and SC 75.6 ± 3.5 vs. 89.3 ± 4.2), which was also associated with the greatest change (expressed in % relative to baseline) in EMG amplitude (healthy vs. NP for SCM 206.6 ± 50.4 vs. 115.9 ± 15.7 and SC 83.4 ± 19.2 vs. 69.2 ± 10.9) across all postural perturbations types. Individuals with NP display altered neural control of the neck musculature in response to rapid, unanticipated full body postural perturbations. Although the relative timing of neck musculature activity in individuals with NP appears to be intact, simultaneous co-activation of the neck musculature emerges for unanticipated anterior-posterior postural perturbations.

Features of cortical neuroplasticity associated with multidirectional novel motor skill training: a TMS mapping study.

Given the evidence that the primary motor cortex (MI) consists of subpopulations of upper motor neurons tuned to different directional parameters of a motor movement, this study hypothesized that novel motor skill training involving either a bidirectional or more complex multidirectional tongue-typing movement should produce distinct training-related features of tongue MI neuroplasticity in humans. Novel motor skill training consisted of tongue typing using custom-made intra-oral keypads for 30-min over two consecutive days. The bidirectional keypad consisted of three sensors positioned along the upper palatal midline as a 3 × 1 array, whereas the multidirectional keypad consisted of nine sensors arranged as a 3 × 3 array that was centred along the upper palatal midline. Each sensor corresponded to one letter and participants were asked to type sequences of letters by accurately placing the tongue over the correct sensor. Before and after each training session, excitability of the tongue MI was assessed with transcranial magnetic stimulation (TMS)-motor evoked potentials (MEPs) over 13 motor map sites and TMS-MEP stimulus-response curves were constructed for the first dorsal interosseous (FDI, as an internal control). Tongue-typing performance improved within and across training days for both groups; although bidirectional training displayed greater success. Bidirectional and multidirectional training were associated with increases and decreases in a number of cortical motor map sites from where tongue activity could be evoked, however; multidirectional training was associated with a greater number of cortical motor map sites with increased excitability and a shift in the centre of gravity of the motor map. No effects of training were found on the FDI TMS-MEP stimulus-response curves. This study revealed distinct training-related features of tongue MI neuroplasticity and proposes that a greater amount of functionally related neuronal populations may be 'trained' by the inclusion of different and more complex directional parameters within a novel motor task.

Facilitated Central Pain Mechanisms Across the Menstrual Cycle in Dysmenorrhea and Enlarged Pain Distribution in Women With Longer Pain History.

Dysmenorrhea (DYS), or recurrent menstrual pain, is a highly prevalent pain condition among otherwise healthy women. However, the progression of DYS over time and the influence of the menstrual cycle phases need to be better understood. While the location and distribution of pain have been used to assess pain mechanisms in other conditions, they are unexplored in DYS. Thirty otherwise healthy women with severe DYS and 30 healthy control women were recruited into 3 subgroups (n = 10) according to the length of their menstrual history (<5, 5-15, or>15 years since menarche). The intensity and distribution of menstrual pain were recorded. Pressure pain thresholds at abdominal, hip, and arm sites, pressure-induced pain distribution, temporal summation of pain, and pain intensity after pressure cessation over the gluteus medius were assessed at 3 menstrual cycle phases. Compared with the healthy control women, those with DYS showed lower pressure pain thresholds in every site and menstrual cycle phase (P < .05), enlarged pressure-induced pain areas during menstruations (P < .01), and increased temporal summation and pain intensity after pressure cessation in the overall menstrual cycle (P < .05). Additionally, these manifestations were enhanced during the menstrual and premenstrual phases compared to ovulation in women with DYS (P < .01). Women with long-term DYS demonstrated enlarged pressure-induced pain distribution, enlarged menstrual pain areas, and more days with severe menstrual pain compared to the short-term DYS subgroup (P < .01). Pressure-induced and menstrual pain distributions were strongly correlated (P < .001). These findings suggest that severe DYS is a progressive condition underscored by facilitated central pain mechanisms associated with pain recurrence and exacerbation. PERSPECTIVE: Enlarged pressure-induced pain areas occur in DYS, associated with the length of the condition and the distribution of menstrual pain. Generalized hyperalgesia is present throughout the entire menstrual cycle and intensifies during premenstrual and menstrual phases.

Spatiotemporal patterns of pain distribution and recall accuracy: a dose-response study.

OBJECTIVES: Clinical decisions rely on a patient's ability to recall and report their pain experience. Monitoring pain in real-time (momentary pain) may reduce recall errors and optimize the clinical decision-making process. Tracking momentary pain can provide insights into detailed changes in pain intensity and distribution (area and location) over time. The primary aims of this study were (i) to measure the temporal changes of pain intensity, area, and location in a dose-response fashion and (ii) to assess recall accuracy of the peak pain intensity and distribution seven days later, using a digital pain mapping application. The secondary aims were to (i) evaluate the influence of repeated momentary pain drawings on pain recall accuracy and (ii) explore the associations among momentary and recall pain with psychological variables (pain catastrophizing and perceived stress). METHODS: Healthy participants (N=57) received a low (0.5 ml) or a high (1.0 ml) dose of hypertonic saline (5.8%) injection into the right gluteus medius muscle and, subsequently, were randomized into a non-drawing or a drawing group. The non-drawing groups reported momentary pain intensity every 30-s. Whereas the drawing groups reported momentary pain intensity and distribution on a digital body chart every 30-s. The pain intensity, area (pixels), and distribution metrics (compound area, location, radiating extent) were compared at peak pain and over time to explore dose-response differences and spatiotemporal patterns. All participants recalled the peak pain intensity and the peak (most extensive) distribution seven days later. The peak pain intensity and area recall error was calculated. Pain distribution similarity was determined using a Jaccard index which compares pain drawings representing peak distribution at baseline and recall. The relationships were explored among peak intensity and area at baseline and recall, catastrophizing, and perceived stress. RESULTS: The pain intensity, area, distribution metrics, and the duration of pain were lower for the 0.5 mL than the 1.0 mL dose over time (p<0.05). However, the pain intensity and area were similar between doses at peak pain (p>0.05). The pain area and distribution between momentary and recall pain drawings were similar (p>0.05), as reflected in the Jaccard index. Additionally, peak pain intensity did not correlate with the peak pain area. Further, peak pain intensity, but not area, was correlated with catastrophizing (p<0.01). CONCLUSIONS: This study showed differences in spatiotemporal patterns of pain intensity and distribution in a dose-response fashion to experimental acute low back pain. Unlike pain intensity, pain distribution and area may be less susceptible in an experimental setting. Higher intensities of momentary pain do not appear to influence the ability to recall the pain intensity or distribution in healthy participants. IMPLICATIONS: The recall of pain distribution in experimental settings does not appear to be influenced by the intensity despite differences in the pain experience. Pain distribution may add additional value to mechanism-based studies as the distribution reports do not vary with pain catastrophizing. REC# N-20150052.

Comparing what the clinician draws on a digital pain map to that of persons who have greater trochanteric pain syndrome.

OBJECTIVES: To assess the agreements and differences in pain drawings (pain area, shape and location) between individuals who have greater trochanteric pain syndrome (GTPS) and their clinician. METHODS: In this study, 23 patients with GTPS (21 female, pain duration range 8-24 months) underwent clinical evaluation by a registered physiotherapist. Digital 2d full body pain drawings were independently performed by the clinician during the subjective examination and by the patient following the physical examination. Levels of agreement [LoA] in the pain area were assessed with Bland-Altman plots. Differences in pain drawings were assessed visually by overlaying images, and by quantifying the differences in shape and location with the bounding box, and Jaccard index, respectively. RESULTS: Pain areas (/total pixels of the charts) did not differ in size (LoA mean difference less than -0.5%; range -2.35-1.56%) or shape (bounding box p>0.17). However, there was minimal overlap in location (Jaccard index range 0.09-0.18/1 for perfect overlap). CONCLUSIONS: Patients and the clinician displayed differences in location of pain areas, but not size or shape, when they independently performed digital pain drawings. The reasons that underlie and the clinical impact of these differences remains unclear.

Modifiable motion graphics for capturing sensations.

OBJECTIVE: The purpose of this study was to assess the relationship between an embodied sensory experience and the ability to translate the perception of this experience visually using modifiable motion graphics. METHODS: A custom-designed software was developed to enable users to modify a motion graphic in real-time. The motion graphics were designed to depict realistic visualizations of pain quality descriptors, such as tingling and burning. Participants (N = 34) received an electrical stimulation protocol known to elicit sensations of tingling. The protocol consisted of eight stimulation intensities ranging from 2-6mA delivered, in a randomized fashion and repeated three times, to the index finger. Immediately after each stimulus, participants drew the area of the evoked sensation on a digital body chart of the hand. Participants then modified the motion graphic of tingling by adjusting two parameters, namely the speed (rate of dots disappearing and re-appearing) and density of these dots in the drawn area. Then, participants rated the perceived intensity and selected the most appropriate pain quality descriptor. RESULTS: There was an increase in the area, density, and perceived intensity ratings as the electrical stimulation intensity increased (P<0.001). The density of the motion graphic, but not speed, correlated with perceived intensity ratings (0.69, P<0.001) and electrical stimulation intensities (0.63, P<0.01). The descriptor 'tingling' was predominantly selected in the range of 3-4.5mA and was often followed by 'stabbing' as the electrical intensity increased. DISCUSSION: The motion graphic tested was perceived to reflect a tingling sensation, the stimulation protocol elicited a tingling sensation, and participants adjusted one of the two motion graphic features systematically. In conclusion, an embodied sensation, such as tingling, maybe visually represented similarly between individuals. These findings create research, clinical, and commercial opportunities that utilize psychophysics to explore, visualize, and quantify changes in embodied sensory experiences in response to known stimuli.

Local hyperalgesia, normal endogenous modulation with pain report beyond its origin: a pilot study prompting further exploration into plantar fasciopathy.

Background and aims Persistent tendinopathies were previously considered solely as peripheral conditions affecting the local tendinous tissue until quantitative sensory testing identified involvement of altered pain processing. In similar fashion, pain in patients with persistent plantar fasciopathy may also involve more than local tissue. The aim of this pilot study was to investigate potential differences in conditioned pain modulation and pressure and thermal pain thresholds, between individuals with PF and healthy pain-free controls, as a precursor to a larger-scale study. Methods We assessed 16 individuals with plantar fasciopathy and 11 pain-free controls. Plantar fasciopathy diagnosis was: palpation pain of the medial calcaneal tubercle or the proximal plantar fascia, duration ≥3 months, pain intensity ≥2/10, and ultrasound-measured plantar fascia thickness ≥4 mm. Quantitative sensory tests were performed locally at the plantar heel and remotely on the ipsilateral elbow. Assessments included pain thresholds for pressure, heat and cold, and conditioned pain modulation measured as change in local resting pressure pain threshold with cold water hand immersion. Participants rated pain intensity at pain threshold. Additionally, the area and distribution of plantar fasciopathy pain was drawn on a digital body chart of the lower limbs. Descriptive analyses were performed and between-group differences/effects expressed as standardised mean differences (d). Results There was no conditioned pain modulation difference between participants with plantar fasciopathy and controls (d = 0.1). Largest effects were on local pressure pain threshold and reported pain intensity on pressure pain threshold (d > 1.8) followed by pain intensity for heat and cold pain thresholds (d = 0.3-1.5). According to the digital body chart, pain area extended beyond the plantar heel. Conclusions The unlikelihood of a difference in conditioned pain modulation yet a pain area extending beyond the plantar heel provide a basis for exploring altered pain processing in a larger-scale study. Implications This was the first study to investigate the presence of altered pain processing in individuals with plantar fasciopathy using a conditioned pain modulation paradigm and thermal pain thresholds. We found no indication of an altered pain processing based on these measures, however, patients rated pain higher on thresholds compared to controls which may be important to clinical practice and warrants further exploration in the future.

Vascular and psychophysical effects of topical capsaicin application to orofacial tissues.

AIMS: To characterize and contrast human sensory and vascular changes produced by topical application of the algesic chemical capsaicin to the glabrous lips and tongue. METHODS: Applications of 1% capsaicin or vehicle cream to the glabrous lips and tongue were randomized between two two-trial sessions. The capsaicin trial followed the vehicle trial for each session. Before and 5, 15, and 30 minutes after capsaicin or vehicle cream application, six parameters were recorded from the glabrous lips or the tongue dorsum: (1) burning pain intensity, as measured on a visual analog scale; (2) burning pain area, as indicated by subjects on an orofacial drawing; (3) mechanical sensitivity, as measured by a von Frey filament; (4) visual flare; (5) blood flow and temperature, as measured by laser-Doppler imaging and thermography, respectively; and (6) areas of increased temperature (hot spots), as calculated by a digital tracer from the thermographs. Data were analyzed by ANOVAs and Pearson's correlations. RESULTS: Compared to vehicle application, capsaicin elicited burning pain, increases in blood flow and temperature, but no change in mechanical sensitivity in the glabrous lips or tongue. Greater increases in blood flow and temperature paralleled more intense burning pain and larger areas of perceived pain for the lips compared to the tongue. The location of distinct areas of increased temperature within the orofacial area differed between the capsaicin-lip and capsaicin-tongue trials. CONCLUSION: The several differences between these responses to noxious stimulation of the glabrous lips and tongue may have implications for examinations of orofacial somatosensory functions.

Enlarged Areas of Pain and Pressure Hypersensitivityby Spatially Distributed Intramuscular Injections ofLow-Dose Nerve Growth Factor.

Intramuscular injection of nerve growth factor (NGF) causes muscle hyperalgesia without immediate pain. This double-blinded, randomized study assessed pain and muscle hypersensitivity after a single-site bolus NGF injection (5 µg) compared with 5 spatially distributed, low-dose NGF injections (1 µg, 4 cm distance) into the tibialis anterior (TA) muscles in 20 healthy subjects. Injection pain was rated on a visual analog scale. Reports of muscle pain with functional tasks (Likert scale score) and the presence of spontaneous pain were collected daily by using a diary. Pressure pain threshold (PPT), overall pain intensity (numerical rating scale), and pain areas following the TA contraction were collected at baseline; 3 hours; and 1, 3, 7, 14, and 21 days postinjection. Low immediate visual analog scale scores were associated with both injection protocols. Likert scale scores showed moderate pain intensities but no spontaneous pain, until day 12, for both injection protocols (P < .05). Reduced PPTs at the 5- and 1-µg injection sites were found after 3 hours, lasting until day 7 (P < .05). The 1-µg injection provoked decreased PPTs at day 1 (P = .036) at the proximal injection site and at day 1 (P = .02) and day 3 (P = .01) at the distal injection site. The TA muscle contraction resulted in larger pain areas and higher numerical rating scale scores at day 3 for the distributed injections compared with the single-site injection (P < .001). Perspective: Spatially distributed low-dose NGF injections induced prolonged pain, mechanical muscle hypersensitivity, and enlarged contraction-evoked pain areas. These features mirror some clinical muscle pain conditions in which diffuse pain areas and muscle hypersensitivity are present during the activities of daily living. Low-dose NGF injections may be useful for further studies of prolonged pain conditions.

Capturing patient-reported area of knee pain: a concurrent validity study using digital technology in patients with patellofemoral pain.

BACKGROUND: Patellofemoral pain (PFP) is often reported as a diffuse pain at the front of the knee during knee-loading activities. A patient's description of pain location and distribution is commonly drawn on paper by clinicians, which is difficult to quantify, report and compare within and between patients. One way of overcoming these potential limitations is to have the patient draw their pain regions using digital platforms, such as personal computer tablets. OBJECTIVE: To assess the validity of using computer tablets to acquire a patient's knee pain drawings as compared to paper-based records in patients with PFP. METHODS: Patients (N = 35) completed knee pain drawings on identical images (size and colour) of the knee as displayed on paper and a computer tablet. Pain area expressed as pixel density, was calculated as a percentage of the total drawable area for paper and digital records. Bland-Altman plots, intraclass correlation coefficient (ICC), Pearson's correlation coefficients and one-sample tests were used in data analysis. RESULTS: No significant difference in pain area was found between the paper and digital records of mapping pain area (p = 0.98), with the mean difference = 0.002% (95% CI [-0.159-0.157%]). A very high agreement in pain area between paper and digital pain drawings (ICC = 0.966 (95% CI [0.93-0.98], F = 28.834, df = 31, p < 0.001). A strong linear correlation (R2 = 0.870) was found for pain area and the limits of agreement show less than ±1% difference between paper and digital drawings. CONCLUSION: Pain drawings as acquired using paper and computer tablet are equivalent in terms of total area of reported knee pain. The advantages of digital recording platforms, such as quantification and reporting of pain area, could be realized in both research and clinical settings.

Experimental Referred Pain Extends Toward Previously Injured Location: An Explorative Study.

Facilitated pain mechanisms have been demonstrated in musculoskeletal pain, but it is unclear whether a recent painful injury leaves the pain system sensitized. Pain characteristics were assessed in individuals who recently recovered from ankle pain (recovered pain group; n = 25) and sex-matched control subjects (n = 25) in response to tonic pressure pain and saline-induced pain applied at the shin muscle. Pain intensity and pain referral patterns were recorded bilaterally after the painful muscle stimulus. Pressure pain thresholds were measured at the lower legs and shoulder. Cuff pressure algometry on the lower leg was used to assess pain detection threshold, pressure evoking 6-cm pain score on a 10-cm visual analog scale, pain tolerance, temporal summation of pain, and conditioned pain modulation. Compared with in control subjects, saline-induced and pressure-induced pain in the shin muscle were more frequently felt as referred pain in the previously painful ankle (P < .05), and the pain area within the previously affected ankle was larger after saline-induced pain (P < .05). In the recovered pain group, conditioned pain modulation responses and the cuff pressure needed to reach a 6-cm pain score on a 10-cm visual analog scale was higher in the previously painful leg compared with in the contralateral leg (P < .05). No group differences were found in pressure pain threshold, pain detection threshold, pain tolerance, and temporal summation of pain. PERSPECTIVE: These explorative findings demonstrate that pain mechanisms responsible for pain location may be reorganized and continue to be facilitated despite recovery. A large prospective study is needed to clarify the time profile and functional relevance of such prolonged facilitation in the pain system for understanding recurring pain conditions.

Distinct patterns of variation in the distribution of knee pain.

The patient's expression of pain using digital-body maps expands analytic opportunities for exploring the spatial variation of bodily pain. A common knee pain condition in adolescents and adults is patellofemoral pain (PFP) and recently PFP was shown to be characterized by a heterogeneous distribution of pain. Whether there are important patterns in these distributions remains unclear. This pioneering study assesses the spatial variation of pain using principal component analysis and a clustering approach. Detailed digital-body maps of knee pain were drawn by 299 PFP patients of mixed sex, age, and pain severity. Three pain distribution patterns emerged resembling an Anchor, Hook, and an Ovate shape on and around the patella. The variations in pain distribution were independent of sex, age, and pain intensity. Bilateral pain associated with a longer duration of pain and the majority characterized by the Hook and Ovate pain distributions. Bilateral and/or symmetrical pain between the left and right knees may represent symptoms associated with longstanding PFP. The distinct patterns of pain location and area suggest specific underlying structures cannot be ruled out as important drivers, although central neuronal mechanisms possibly exemplified by the symmetrical representation of pain may play a role in individuals with longstanding symptoms.