Pain referral and regional deep tissue hyperalgesia in experimental human hip pain models

Hip disorder patients typically present with extensive pain referral and hyperalgesia. To better understand underlying mechanisms, an experimental hip pain model was established in which pain referrals and hyperalgesia could be studied under standardized conditions. In 16 healthy subjects, pain was induced by hypertonic saline injection into the gluteus medius tendon (GMT), adductor longus tendon (ALT), or gluteus medius muscle (GMM). Isotonic saline was injected contralaterally as control. Pain intensity was assessed on a visual analogue scale (VAS), and subjects mapped the pain distribution. Before, during, and after injections, passive hip joint pain provocation tests were completed, together with quantitative sensory testing as follows: pressure pain thresholds (PPTs), cuff algometry pain thresholds (cuff PPTs), cutaneous pin-prick sensitivity, and thermal pain thresholds. Hypertonic saline injected into the GMT resulted in higher VAS scores than hypertonic injections into the ALT and GMM (P < .05). Referred pain areas spread to larger parts of the leg after GMT and GMM injections compared with more regionalized pain pattern after ALT injections (P < .05). PPTs at the injection site were decreased after hypertonic saline injections into GMT and GMM compared with baseline, ALT injections, and isotonic saline. Cuff PPTs from the thigh were decreased after hypertonic saline injections into the ALT compared with baseline, GMT injections, and isotonic saline (P < .05). More subjects had positive joint pain provocation tests after hypertonic compared with isotonic saline injections (P < .05), indicating that this provocation test also assessed hyperalgesia in extra-articular soft tissues. The experimental models may open for better understanding of pain mechanisms associated with painful hip disorders.     

The analgesic effects of interferential therapy on two experimental pain models: cold and mechanically induced pain

Objective

To evaluate the analgesic effects of interferential therapy (IFT) when using cold and mechanical pain models. The aim was to determine whether the effects of IFT are dependent on the origin of experimental pain.

Design

Randomised controlled trail.

Setting

University research laboratory.

Participants

Twenty pain-free participants.

Intervention

Each participant was exposed to the two methods of pain induction on different days.

Main outcome measures

Cold pain threshold (time to first sensation of pain), intensity and unpleasantness measured on a visual analogue scale (VAS); mechanical pain threshold (tolerance to pressure) and unpleasantness (VAS).

Results

IFT produced similar effects on the threshold (first sensation of pain) for both cold and mechanical pain. The thresholds were significantly increased and the percentage changes in both were similar, as were their standard deviations. This indicates that the analgesia provided by IFT is similar whether the origin of pain is cold or mechanical, and suggests that IFT can affect pain from a range of origins. The effect of IFT on other measures was not as pronounced. With mechanical pain, neither pain tolerance (maximum tolerable pain) nor unpleasantness was significantly altered. With cold pain, both intensity and unpleasantness showed a small but statistically significant change.

Conclusions

The cold and mechanical pain models are equally effective experimental tools to investigate electroanalgesia. These findings also suggest that future research should not induce pain beyond threshold when using the cold and mechanical pain models, as little additional information is gathered whilst subject discomfort and the risk of tissue damage is increased.     

Repeated intramuscular injections of nerve growth factor induced progressive muscle hyperalgesia,facilitated temporal summation,and expanded pain areas

Intramuscular injection of nerve growth factor (NGF) is known to induce deep-tissue mechanical hyperalgesia. In this study it was hypothesised that daily intramuscular injections of NGF produce a progressive manifestation of soreness, mechanical hyperalgesia, and temporal summation of pain. In a double-blind placebo-controlled design, 12 healthy subjects were injected on 3 days with NGF into the tibialis anterior muscle and with isotonic saline on the contralateral side. Assessments were performed before and after the injections on days 0, 1, and 2, and repeated on days 3, 6, and 10. The self-perceived muscle soreness was assessed on a Likert scale. Computer-controlled pressure algometry was used to assess the pressure pain thresholds (PPTs). Temporal summation of pain after repeated pressure stimulations was assessed by computer-controlled pressure algometry. The pain distribution following painful pressure stimulation was also recorded. Compared with baseline and isotonic saline, the NGF injections caused (P < 0.05): (1) progressively increasing soreness scores from 3 hours after the first injection until day 2, after which it remained increased; (2) decreased PPTs at days 1 to 3; (3) facilitated temporal summation of pressure pain at days 1 to 10; and (4) enlarged pressure-induced pain area after the injection on day 1 to day 6. The daily injections of NGF produced a progressive manifestation of muscle soreness, mechanical hyperalgesia, temporal summation of pressure pain, and pressure-induced pain distribution. These data illustrate that the prolonged NGF application affects peripheral and central mechanisms and may reflect process in musculoskeletal pain conditions.     

Tetrodotoxin inhibits the development and expression of neuropathic pain induced by paclitaxel in mice

We evaluated the effect of low doses of systemically administered tetrodotoxin (TTX) on the development and expression of neuropathic pain induced by paclitaxel in mice. Treatment with paclitaxel (2 mg/kg, i.p., once daily during 5 days) produced long-lasting (2–4 weeks) heat hyperalgesia (plantar test), mechanical allodynia (electronic Von Frey test) and cold allodynia (acetone drop method), with maximum effects observed on days 7, 10 and 10–14, respectively. Acute subcutaneous treatment with 1 or 3 μg/kg of TTX reduced the expression of mechanical allodynia, whereas higher doses (3 or 6 μg/kg) were required to reduce the expression of cold allodynia and heat hyperalgesia. In contrast, TTX (3 or 6 μg/kg, s.c.) did not affect the response to the same thermal and mechanical stimuli in control animals, which indicates that the antihyperalgesic and antiallodynic effects of TTX were not due to unspecific inhibition of the perception of these stimuli. Administration of TTX (6 μg/kg, s.c.) 30 min before each of the 5 doses of paclitaxel did not modify the development of heat hyperalgesia produced by the antineoplastic, but abolished the development of mechanical and cold allodynia. Coadministration of a lower dose of TTX (3 μg/kg) also prevented the development of mechanical allodynia. No signs of TTX-induced toxicity or motor incoordination were observed. These data suggest that low doses of TTX can be useful to prevent and treat paclitaxel-induced neuropathic pain, and that TTX-sensitive subtypes of sodium channels play a role in the pathogenesis of chemotherapy-induced neuropathic pain.     

Plantarflexor muscle function in healthy and chronic Achilles tendon pain subjects evaluated by the use of EMG and PET imaging

Background

Achilles tendon pathologies may alter the coordinative strategies of synergistic calf muscles. We hypothesized that both surface electromyography and positron emission tomography would reveal differences between symptomatic and asymptomatic legs in Achilles tendinopathy patients and between healthy controls.

Methods

Eleven subjects with unilateral chronic Achilles tendon pain (28 years) and eleven matched controls (28 years) were studied for triceps surae and flexor hallucis longus muscle activity in response to repetitive isometric plantarflexion tasks performed at 30% of maximal voluntary contraction using surface electromyography and glucose uptake using positron emission tomography. Additionally, Achilles tendon glucose uptake was quantified.

Findings

Normalized myoelectric activity of soleus was higher (P < 0.05) in the symptomatic leg versus the contralateral and control legs despite lower absolute force level maintained (P < 0.005). Electromyography amplitude of flexor hallucis longus was also greater on the symptomatic side compared to the healthy leg (P < 0.05). Both the symptomatic and asymptomatic legs tended to have higher glucose uptake compared to the control legs (overall effect size: 0.9 and 1.3, respectively). Achilles tendon glucose uptake was greater in both legs of the patient group (P < 0.05) compared to controls. Maximal plantarflexion force was ~ 14% greater in the healthier leg compared to the injured leg in the patient group.

Interpretations

While the electromyography showed greater relative amplitude in the symptomatic leg, the results based on muscle glucose uptake suggested relatively similar behavior of both legs in the patient group. Higher glucose uptake in the symptomatic Achilles tendon suggests a higher metabolic demand.     

Experimental muscle pain provokes long-lasting alterations of thermal sensitivity in the referred pain area.

This study explores thermal sensitivity and thermal nociception for signs of central sensitization in the area of referred muscle pain. Two groups of 24 healthy subjects (ss) each, and with mean ages of, respectively, 27 and 55 years, were first trained in quantitative sensory testing and pain rating. Then, in a second session, referred pain was evoked by injection of 6% hypertonic saline into the infraspinatus muscle. Cold and warm thresholds, synthetic heat threshold (SHT--evoked by an alternating pattern of adjacent cold and warmth), and thermal pain thresholds were measured within the referred pain area at a rate of 1/20 min for 60-120 min. All ss of both groups experienced referred pain mostly in the upper arm and of medium intensity. Pain lasted for approximately 12min with a shorter duration in the older group (p<0.02). The cold threshold increased significantly (p<0.001), and the warm threshold slightly, after the injection and remained high for the whole observation period (i.e. lower and higher temperatures were necessary to elicit cold and warmth, respectively). Threshold recovery was more delayed in the older age group. Of those 28 ss in whom cold pain threshold could be followed during the whole observation period, 18 ss showed an immediate threshold decrease of average 6 degrees C which outlasted the observation period. Four ss responded with a threshold increase. Heat pain thresholds were not affected in the referred pain area. Average synthetic heat threshold did not change; there were, however, distinct and lasting individual threshold shifts in either direction. Ss with lowered cold pain thresholds or evident threshold shifts for synthetic heat had also higher pain ratings. The results demonstrate that experimental muscle pain can induce long-lasting changes in thermal sensitivity and nociception. The unexpected cold threshold increase may tentatively be explained as an expression of long-term depression. The decrease of cold pain threshold or SHT in subgroups of ss may indicate central sensitization. However, the observed changes in this experiment do not provide an unambiguous indicator for central sensitization which seems to be rather individual and might depend on pain intensity and proneness to express central mechanisms of sensitization. Therefore in clinical pain states the individual pattern of sensory abnormalities has to be analysed and interpreted in addition to the pain parameters to assess central involvement.     

Experimental pain by ischaemic contractions compared with pain by intramuscular infusions of adenosine and hypertonic saline.

Deep tissue pain can be related to reduced muscle blood flow, which comprises the metabolic demand under muscle work. The tissues and receptors involved in nociception after ischaemic muscle contractions are not known. The concentration of adenosine is increased after ischaemic contractions and might act as an algesic substance. In 15 subjects, adenosine, hypertonic saline (algesic), and isotonic mannitol (placebo) were infused into the tibialis anterior muscle and compared with the pain caused by ischaemic contractions. The muscle pain intensity (visual analogue scale; VAS), distribution, and quality were assessed. Pressure pain thresholds were recorded to assess the deep tissue sensitivity. Adenosine did not induce more pain than the placebo. The maximal VAS score after hypertonic saline and ischaemic contractions was higher compared with adenosine/placebo infusions. The duration and area of pain were significantly increased after hypertonic saline infusions compared with ischaemic contractions. Higher scores on the McGill pain questionnaire were given to the "stabbing", "burning", "heavy", and "exhausting" word categories after ischaemic contractions, and "cramping" was rated higher during hypertonic saline-induced muscle pain compared with ischaemic contractions. During hypertonic saline infusions, the pressure pain threshold was decreased compared with before and immediately after the pain had vanished. The present study shows that pharmacological levels of adenosine in skeletal muscle did not induce pain. Excitation of muscle nociceptors by hypertonic saline evoked hyperalgesia, larger areas of pain, and a different quality of pain compared with ischaemic contractions, suggesting that the pain after ischaemic contractions is mediated by other populations of nociceptors in muscle and/or other tissues than excited by hypertonic saline.     

Acute experimental endotoxemia induces visceral hypersensitivity and altered pain evaluation in healthy humans

Growing evidence suggests that systemic immune activation plays a role in the pathophysiology of pain in functional bowel disorders. By implementing a randomized crossover study with an injection of endotoxin or saline, we aimed to test the hypothesis that endotoxin-induced systemic inflammation increases visceral pain sensitivity in humans. Eleven healthy men (mean ± standard error of the mean age 26.6 ± 1.1 years) received an intravenous injection of either lipopolysaccharide (LPS; 0.4 ng/kg) or saline on 2 otherwise identical study days. Blood samples were collected 15 min before and 1, 2, 3, 4, and 6h after injection to characterize changes in immune parameters including proinflammatory cytokines. Rectal sensory and pain thresholds and subjective pain ratings were assessed with barostat rectal distensions 2h after injection. LPS administration induced an acute inflammatory response indicated by transient increases in tumor necrosis factor alpha, interleukin 6, and body temperature (all P<.001). The LPS-induced immune activation increased sensitivity to rectal distensions as reflected by significantly decreased visceral sensory and pain thresholds (both P<.05) compared to saline control. Visceral stimuli were rated as more unpleasant (P<.05) and inducing increased urge to defecate (P<.01). Pain thresholds correlated with interleukin 6 at +1h (r=0.60, P<.05) and +3h (r=0.67, P<.05) within the LPS condition. This report is novel in that it demonstrates that a transient systemic immune activation results in decreased visceral sensory and pain thresholds and altered subjective pain ratings. Our results support the relevance of inflammatory processes in the pathophysiology of visceral hyperalgesia and underscore the need for studies to further elucidate immune-to-brain communication pathways in gastrointestinal disorders.     

Comparison of pain and dyspnea perceptual responses in healthy subjects

Dyspnea and pain have a number of similarities. Recent brain imaging experiments showed that similar cortical regions are activated by the perceptions of dyspnea and pain. We tested the hypothesis that an individual’s pain sensitivity might parallel the individual’s dyspnea sensitivity. Studies were carried out in 52 young healthy subjects. Each subject experienced experimentally induced pain and dyspnea. Pain was induced by a cold-pressor test and dyspnea was induced by breathholding while the unpleasant experience of pain and dyspnea was assessed by using a Visual Analogue Scale (VAS). The times from the start of cold stimulation and breathholding to the onset of uncomfortable sensation (pain threshold time and the period of no respiratory sensation, respectively) and to the limit of tolerance (pain endurance time and total breathholding time, respectively) were also measured. In response to cold pain stimulation, a behavioral dichotomy (pain-tolerant and pain-sensitive) was observed. The period of no respiratory sensation was significantly shorter in the PS (pain-sensitive) group than in the PT (pain-tolerant) group (16.9 ± 3.8 vs. 19.6 ± 5.3 s: P < 0.05), whereas no significant difference in the total breathholding time was found between the PT and PS groups. A significant correlation was observed between the pain threshold time and the period of no respiratory sensation in both the PT and PS groups. However, no significant association was observed between pain and dyspnea tolerance in both groups. In conclusion, an individual’s pain threshold is correlated to the individual’s dyspnea threshold, but the individual’s pain tolerance is not consistently correlated to the individual’s dyspnea tolerance.     

Hypoalgesia to pressure pain in referred pain areas triggered by spatial summation of experimental muscle pain from unilateral or bilateral trapezius muscles

Animal and human experimental studies have suggested the importance of spatial summation in the nociception processing and in the activation of descending inhibition. However, the relationship between the areas (size) of muscles stimulated and the recruitment of descending inhibition has not been addressed. Consequently, we tested whether bilateral versus unilateral injection of hypertonic saline into trapezius muscles caused hypoalgesia to pressure pain (pressure pain thresholds, PPTs) in the local pain areas (the trapezius muscles) and the referred pain areas (the posterolateral neck muscles). Two groups of volunteers participated. One group received a unilateral injection (one injection) and the other group bilateral injections (two injections). In the bilateral group, hypertonic saline was injected in one trapezius first, and 45 s later, while pain was still present from the first injection, a second injection was performed into the contralateral trapezius muscle. The saline-evoked time to maximal pain was significantly shorter after the second injection than after the first injection. More subjects developed referred pain after the bilateral compared with the unilateral injection. In the referred pain areas, the PPTs 7.5 and 15 min after the second injection were significantly increased compared with the first injection, while no changes in the PPT were observed in local and referred pain areas after unilateral injection. This suggests that the induction of descending inhibition was triggered by spatial summation during the later phase of experimentally induced muscle pain. The present experimental model might be used for further investigation of descending inhibition related to the spatial characteristics of nociceptive stimuli in humans.     

吗啡超前镇痛对阑尾手术内脏牵拉痛的影响

目的探讨吗啡硬膜外超前镇痛对抑制阑尾手术内脏牵拉痛及术后镇痛情况的影响。方法 40例ASAⅠ～Ⅱ级急、慢性阑尾炎患者,均于硬膜外麻醉下行阑尾切除术。将其随机分为两组,每组20例,即Ⅰ组（对照组）：术前不施行超前镇痛;Ⅱ组（实验组）：切皮前10 min将吗啡1.5 mg加入利多卡因注入硬膜外腔。所有患者均不行术后镇痛。观察两组患者术中牵拉反应、术后疼痛情况及并发症。结果Ⅱ组抑制术中牵拉痛的效果明显优于I组（P〈0.05）;Ⅱ组首次出现疼痛时间较Ⅰ组显著延长（P〈0.01）,Ⅱ组术后尿潴留患者多于Ⅰ组（P〈0.01）。结论吗啡硬膜外超前镇痛能明显抑制术中牵拉痛,提供良好的术后镇痛效果,减少阿片类药物的用量。     

Stress coping strategies in thermal pain sensitive and insensitive healthy subjects

The aim of this study was to investigate stress coping strategies used in relation to heat and cold pain thresholds in healthy subjects. After using the Jalowiec Coping Scale, cold and heat pain thresholds were examined using the Quantitative Somatosensory Test in 47 healthy subjects. The participants were separated into thermal pain sensitive and insensitive groups, based on thermal pain perception. The results showed that subjects sensitive to thermal pain tended to adopt an emotive stress coping style significantly more commonly than the insensitive subjects. Furthermore, women displayed a marked preference for this style compared to men. The conclusion is that emotional stress coping did play a role in the perception of thermal pain in this group of healthy subjects and that clinical nursing interventions need to focus on the relationship between emotion and coping.     

Referred sensations and neuropathic pain following spinal cord injury

It has been proposed that painful and non-painful referred sensations (RSs) are associated with reorganization of sensory pathways in patients with complete spinal cord injury (SCI). In order to investigate the referred sensation (RS) phenomenon and its correlation with neuropathic pain (NP) 48 patients with complete SCI, 24 with chronic NP and 24 without pain or paraesthesias were studied using clinical examination and neurophysiological tests. Patients reporting RSs were re-examined at 2 and 10 weeks after the first examination. We defined the presence of RS as sensations perceived below the injury level in response to touch and pinprick stimuli in various body points above the injury level. The examination was carried out by one researcher applying the stimuli to the patient under two visual conditions (open and closed eyes), and then asking the patient to make tactile self-stimulation. Seven patients with SCI and NP (29%) reported RS below the injury level. RS were well located and consistently evoked at repeated examinations. Touch and pinprick stimulation elicited similar RS that were non-painful in six patients and painful in one. Visual feedback did not change RS perception and characteristics. None of the patients in the SCI group without NP presented RS. In conclusion, our results indicate that RS is relatively frequent in patients with complete SCI and NP. The common occurrence of RS in patients with NP and the location of the sensations in the same area as NP suggest that pain and RS share common pathophysiological mechanisms.     

Experimental human muscle pain induced by intramuscular injections of bradykinin,serotonin, and substance P

After intramuscular (m. tibialis anterior) injection of three different algogenic substances, the pain intensity was continuously scored on a visual analogue scale (VAS) in eight volunteers. The subject drew the distribution of the local and referred pain areas on a map. Four times within the first hour after injection, the pressure pain–thresholds (PPTs) and supra pressure–pain thresholds were assessed at the injection point, 2 cm distal from the injection site, at the arm, and at the contralateral leg. Measurements were done before and after injection of 0.5 ml of the algogenic substance [bradykinin (BKN), serotonin (5-HT), substance P (SP)], and isotonic saline as control. Cutaneous sensitivity to mechanical stimuli was assessed with a Von Frey hair at the same location as PPT determinations. The pain intensity (VAS-peak) after BKN (2, 4, and 10 nmol) and 5-HT (2, 4, and 20 nmol) was significantly higher (p< 0.05) than after SP (0.2, 0.4, and 0.8 nmol) and isotonic saline. The VAS-peak after infusions of hypertonic saline was significantly higher (p< 0.05) compared with VAS-peaks after all other substances. A significantly larger (p< 0.05) local pain area was found after BKN compared with isotonic saline. After injections of hypertonic saline, the offsets of evoked pain were significantly longer (p< 0.05) and the local and referred pain areas were significantly larger (p< 0.05) compared with all other substances. There was no dose–response relation between the pain intensity and the different doses of BKN, 5-HT, and SP. PPTs and skin sensitivity were not affected by any of the injections. We conclude that under the present experimental conditions, BKN and 5-HT can produce low levels of muscle pain after intramuscular injection. In the used concentrations, however, BKN, 5-HT, and SP did not generate cutaneous or muscular hyperalgesia.     

Characteristics of referred muscle pain to the head from active trigger points in women with myofascial temporomandibular pain and fibromyalgia syndrome

Our aim was to compare the differences in the prevalence and the anatomical localization of referred pain areas of active trigger points (TrPs) between women with myofascial temporomandibular disorder (TMD) or fibromyalgia (FMS). Twenty women (age 46 ± 8 years) with TMD and 20 (age 48 ± 6 years) with FMS were recruited from specialized clinic. Bilateral temporalis, masseter, sternocleidomastoid, upper trapezius, and suboccipital muscles were examined for TrPs. TrPs were identified by palpation and considered active when the pain reproduced familiar pain symptom experienced by the patient. The referred pain areas were drawn on anatomical maps, digitalized and also measured. A new analysis technique based on a center of gravity (COG) method was used to quantitative estimate of the localization of the TrP referred pain areas. Women with FMS exhibited larger areas of usual pain symptoms than women with myofascial TMD (P < 0.001). The COG coordinates of the usual pain on the frontal and posterior pain maps were located more superior in TMD than in FMS. The number of active TrPs was significantly higher in TMD (mean ± SD 6 ± 1) than in FMS (4 ± 1) (P = 0.002). Women with TMD exhibited more active TrPs in the temporalis and masseter muscles than FMS (P < 0.01). Women with FMS had larger referred pain areas than those with TMD for sternocleidomastoid and suboccipital muscles (P < 0.001). Significant differences within COG coordinates of TrP referred pain areas were found in TMD, the referred pain was more pronounced in the orofacial region, whereas the referred pain in FMS was more pronounced in the cervical spine. This study showed that the referred pain elicited from active TrPs shared similar patterns as usual pain symptoms in women with TMD or FMS, but that distinct differences in TrP prevalence and location of the referred pain areas could be observed. Differences in location of referred pain areas may help clinicians to determine the most relevant TrPs for each pain syndrome in spite of overlaps in pain areas.     

High concurrent validity between digital and analogue algometers to measure pressure pain thresholds in healthy participants and people with migraine: a cross-sectional study

BackgroundPressure pain thresholds (PPTs) are commonly assessed to quantify mechanical sensitivity in various conditions, including migraine. Digital and analogue algometers are used, but the concurrent validity between these algometers is unknown. Therefore, we assessed the concurrent validity between a digital and analogue algometer to determine PPTs in healthy participants and people with migraine.MethodsTwenty-six healthy participants and twenty-nine people with migraine participated in the study. PPTs were measured interictally and bilaterally at the cephalic region (temporal muscle, C1 paraspinal muscles, and trapezius muscle) and extra-cephalic region (extensor carpi radialis muscle and tibialis anterior muscle). PPTs were first determined with a digital algometer, followed by an analogue algometer. Intraclass correlation coefficients (ICC_3.1) and limits of agreement were calculated to quantify concurrent validity.ResultsThe concurrent validity between algometers in both groups was moderate to excellent (ICC_3.1 ranged from 0.82 to 0.99, with 95%CI: 0.65 to 0.99). Although PPTs measured with the analogue algometer were higher at most locations in both groups (p < 0.05), the mean differences between both devices were less than 18.3 kPa. The variation in methods, such as a hand-held switch (digital algometer) versus verbal commands (analogue algometer) to indicate when the threshold was reached, may explain these differences in scores. The limits of agreement varied per location and between healthy participants and people with migraine.ConclusionThe concurrent validity between the digital and analogue algometer is excellent in healthy participants and moderate in people with migraine. Both types of algometer are well-suited for research and clinical practice but are not exchangeable within a study or patient follow-up.     

Basic aspects of musculoskeletal pain: from acute to chronic pain

The transition from acute to chronic musculoskeletal pain is not well understood. To understand this transition, it is important to know how peripheral and central sensitization are manifested and how they can be assessed. A variety of human pain biomarkers have been developed to quantify localized and widespread musculoskeletal pain. In addition, human surrogate models may be used to induce sensitization in otherwise healthy volunteers. Pain can arise from different musculoskeletal structures (e.g. muscles, joints, ligaments, or tendons), and differentiating the origin of pain from those different structures is a challenge. Tissue specific pain biomarkers can be used to tease these different aspects. Chronic musculoskeletal pain patients in general show signs of local/central sensitization and spread of pain to degrees which correlate to pain intensity and duration. From a management perspective, it is therefore highly important to reduce pain intensity and try to minimize the duration of pain.     

Catecholamine-induced excitation of nociceptors in sympathetically maintained pain

Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of several seconds following strong endogenous sympathetic bursts; they were also excited for about 3 min following the injection of norepinephrine (10 microl, 0.05%) into their innervation territory. In these two fibers, a prolonged activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl) and sensitization of their heat response following prostaglandin E2 injection were recorded, evidencing their afferent nature. Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found.     

Sensory information and geographical orientation in healthy subjects

The effect of sensory input on the performance of a geographical orientation task of children at two different ages (kindergartners and fourth graders) and adults was determined. I investigated the ability of subjects to point accurately to the starting position after experiencing identical routes under three sensory conditions. In Condition 1, subjects were led walking through routes and could see the walls and ceiling of the test room (visual, somatosensory, and vestibular information). In Condition 2, subjects were led walking with vision occluded (somatosensory and vestibular information). In Condition 3, subjects were pushed in a wheelchair with vision occluded (primarily vestibular information). As more sensory information was available, subjects maintained their orientation better to their starting position, and accuracy improved with age. This quantitative analysis of geographical orientation may be appropriate for future clinical studies of neurologically impaired adults and children.