PubMed Health⌕ Search

Biomedical subjects

L Arendt-Nielsen

Publications and source records attributed to L Arendt-Nielsen.

At least 19 recordsLinked to original sources

Effect of pre-emptive ketamine on sensory changes and postoperative pain after thoracotomy: comparison of epidural and intramuscular routes.

BACKGROUND: In this study we have evaluated the efficacy of ketamine via i.m. and epidural routes for the control of post-thoracotomy pain. METHODS: The study was randomized, double blinded and placebo controlled. With the approval of the Faculty Ethics Committee, 60 patients undergoing elective thoracotomy were randomized into three equal groups. Group IM had i.m. ketamine 1 mg kg(-1) in 2 ml plus epidural normal saline; Group EPI had epidural ketamine 1 mg kg(-1) in 10 ml plus i.m. normal saline; Group C had epidural normal saline 10 ml plus i.m. normal saline 10 ml. Anaesthesia was standardized. Postoperative analgesia was maintained with epidural patient-controlled analgesia using bupivacaine and morphine. Visual analogue scale values and analgesic consumption were evaluated at 2, 4, 6, 8, 10, 12, 24 and 48 h after surgery. The areas of allodynia, pin-prick hyperalgesia and pressure hyperalgesia were measured at 48 h, and days 15 and 30 in all groups. RESULTS: Intraoperative fentanyl requirement was significantly lower in Group EPI than Group C. The morphine and bupivacaine requirements were significantly lower in Group EPI than the other two groups in the postoperative period. There was reduced pin-prick hyperalgesia and touch allodynia in the EPI group. There were no side-effects attributable to ketamine. CONCLUSION: The results of the present study demonstrate that pre-emptive epidural ketamine is effective in reducing intra- and postoperative analgesic requirements, hyperalgesia and touch allodynia.

Adult↗

Glutamate evoked neck and jaw muscle pain facilitate the human jaw stretch reflex.

OBJECTIVE: Although pain and neuromuscular function are clearly linked in several clinical conditions manifested in the craniofacial and cervical regions, it is unclear if pain in these regions influences reflexly evoked activity in the jaw or neck muscles in humans. The aim of the present study was to test the effects of glutamate-evoked jaw or neck muscle pain on the jaw stretch reflex recorded in both jaw and neck muscles. METHODS: Nineteen healthy men participated in the study. Electromyographic (EMG) recordings were made from the left masseter (MAL) and right masseter (MAR) muscles and the right sternocleidomastoid (SCM) and splenius (SP) muscles. Glutamate (1 M) or isotonic saline was injected into the MAR or right SP in random order and then the other solution was injected 1-3 weeks later. Pain intensity was scored on a 10 cm visual analogue scale. Stretch reflexes were evoked by standardized jaw stretches before, during and 15 min after the end of the experimental muscle pain. Twenty trials were averaged in each condition. RESULTS: Pain evoked by MAR or SP glutamate injections was associated with a significant increase in the stretch reflex amplitude recorded in both MAR and SCM. The onset and offset times and duration of the stretch reflex did not change in any muscle during the various pain conditions. Injection of isotonic saline into the MAR or SP did not produce any significant change in the reflex parameters in any of the muscles. CONCLUSIONS: The results indicate the close interplay between the craniofacial and cervical regions in the neuromuscular changes that may result from musculoskeletal pain in either region. SIGNIFICANCE: The changes in neuromuscular activity documented in this study may be involved in the clinical occurrence of altered muscle activity in the orofacial and cervical regions as a result of deep tissue trauma and pain.

Adult↗

Experimental muscle pain increases trapezius muscle activity during sustained isometric contractions of arm muscles.

OBJECTIVE: In the present study, the influence of experimental muscle pain on muscle co-ordination and fatigue development during sustained isometric elbow flexion was investigated. METHODS: Conventional surface electromyography (EMG) was recorded from the biceps brachii, brachioradialis, deltoideus and trapezius muscle during isometric elbow flexion at 40% maximum force. Single motor unit (MU) conduction velocity in the biceps brachii was assessed using a high spatial resolution surface EMG technique. Measurements were performed on 15 healthy subjects before, during and after (1) injection of hypertonic (pain condition) and (2) isotonic saline (control) into the biceps brachii. The pain intensity was assessed on a 10 cm visual analogue scale. RESULTS: The experimental results showed in both experimental sessions a fatigue-related increase of the root mean square value of EMG (222+/-164% of the baseline), and a decrease of the median frequency (118+/-16% of the baseline) in all investigated muscles. A maximum pain level of in average 3.2 cm on the visual analogue scale was reached after injection of hypertonic saline during contraction. Differences between painful and control condition were seen in an increased trapezius activity (230+/-141%) during pain. The global EMG activity of the brachioradialis and biceps brachii was unaffected by experimental muscle pain in line with unaffected single MU conduction velocity in the biceps brachii. Differences in endurance time (mean 89.3 and 102.3 s, pain and control, respectively) were not significant. CONCLUSIONS/SIGNIFICANCE: The findings suggest that upper extremity pain could be a possible source for overloading the trapezius muscle and as such is an important factor in occupational settings.

Adult↗

Effects of experimental muscle pain on mechanical properties of single motor units in human masseter.

OBJECTIVE: Muscle pain is known to influence muscle activity but the details of its effects on the mechanical properties of single motor units (SMU) have not been described. We have recently reported a decreased firing rate of SMU in the human masseter muscle during painful contractions with a constant force output. Force output can be modulated by the SMU discharge rate in relation to the contractile properties of SMU. Therefore, the objective of the present study was to measure the mechanical properties of SMU in the masseter to clarify the mechanism which underlies the decrease in SMU firing rate during jaw-muscle pain. METHODS: A spike-triggered averaging (STA) technique was used to determine the mechanical properties of low-threshold SMU in the masseter muscle recorded with fine wire electrodes during a voluntary isometric contraction. The twitch amplitude, contraction time, and half-relaxation time were determined from the averaged force records before and during experimental jaw-muscle pain induced by injection of 0.2 ml (100 microg/ml) capsaicin in 8 healthy subjects. Injections of 0.2 ml isotonic saline served as a non-painful control in 11 healthy subjects. RESULTS: The twitch amplitude was significantly increased during capsaicin-evoked muscle pain (P<0.001) without significant changes of half-relaxation time and contraction time. No significant changes in SMU twitch properties were observed during the control injections. CONCLUSIONS: Potentiation of twitch force could be a possible compensatory mechanism to maintain a constant force output during painful isometric contractions when SMU firing decreases. This finding therefore provides new information on the adaptation of motor function by muscle pain.

Adult↗

Somatosensory changes in the referred pain area in patients with acute cholecystitis before and after treatment with laparoscopic or open cholecystectomy.

BACKGROUND: Visceral pain can lead to hypersensitivity in the referred pain area. In patients with chronic visceral pain this somatic hypersensitivity can persist for years. As 25%-40% of patients continue to have symptoms after cholecystectomy, whereof no explanation for pain can be offered in up to 30%, it could be hypothesized that altered sensory characteristics induced by acute cholecystitis could persist in some patients and thus be responsible for postcholecystectomy pain. The aim of this study was to investigate the somatosensory sensitivity in the referred pain area in patients with acute cholecystitis before and after cholecystectomy. METHODS: Patients with acute cholecystitis were studied before (n = 30) and after (n = 18) treatment. Sensitivity to pinprick, heat, cold, pressure and single and repeated electrical stimulation was studied in the referred pain area and in the control area on the contralateral side of the abdomen. RESULTS: Significant hypersensitivity in the referred pain area was detected in patients with acute cholecystitis. The somatic sensitivity was normalized after cholecystectomy. CONCLUSIONS: Acute cholecystitis leads to hypersensitivity in the referred pain area. Persistent hypersensitivity, as earlier reported after chronic visceral pain, was not seen aftiser cholecystectomy, indicating that this mechanism may not play a major role in patients with postcholecystectomy pain syndrome. The possible role in patients operated on for chronic gallstone pain has still to be investigated.

Abdominal Pain↗

A comparison of hyperalgesia and neurogenic inflammation induced by melittin and capsaicin in humans.

Melittin (a main compound of bee venom) and capsaicin were injected intradermally in healthy human volunteers: (1) to study secondary mechanical hyperalgesia (static hyperalgesia and dynamic hyperalgesia) around the injection site; and (2) to correlate the sensory changes to the neurogenic inflammation assessed by laser-doppler blood flowmetry. Melittin 50 microg and capsaicin 10 microg induced comparable spontaneous pain and increased blood flow (neurogenic inflammation). Intradermal injection of melittin induced regions of secondary mechanical hyperalgesia around the injection site, however, they were not as large as the hyperalgesia induced by capsaicin. This is the first report studying mechanical hyperalgesia induced by melittin in humans, and the results were in agreement with the previous observations in rats. Melittin seems to be a valuable model to study a possible contribution of neurogenic inflammation to hyperalgesia in humans.

Analysis of Variance↗

[Assessment of muscle pain and hyperalgesia. Experimental and clinical findings].

AIM: It is evident that muscle hyperalgesia and referred pain have an important role in chronic musculoskeletal pain. More knowledge of the basic mechanisms involved and better methods of assessing muscle pain in clinical practice are needed so that treatment regimens can be revised and improved. METHODS: Methods of quantitative sensory testing of muscle pain and associated phenomena are described. These methods make it possible to evaluate manifestations of muscle pain in a standardised way both in patients suffering from musculoskeletal pain and in healthy volunteers. RESULTS: Elevated muscle sensitivity becomes manifest as (1) pain evoked by a normally non-noxious stimulus (allodynia), (2) abnormally intense pain evoked by noxious stimuli (hyperalgesia), or (3) unusually large areas of referred pain with associated somatosensory changes. These changes can occur as increased somatosensory sensitivity of deep somatic tissues or of the skin in areas of pain referral. Some manifestations of sensitisation in chronic musculoskeletal pain patients, such as expansion of the areas of referred muscle pain, can be explained by the extra segmental spread of central sensitisation seen in animal experiments. CONCLUSIONS: An important part of the manifestations of pain in chronic musculoskeletal disorders may be due to peripheral and central sensitisation processes, which are also involved in the transition from acute to chronic pain. Knowledge of these processes has expanded enormously in recent years; it should be utilised when new intervention strategies are designed.

Humans↗

Lasers and other thermal stimulators for activation of skin nociceptors in humans.

Pain can be induced by thermal, chemical, and mechanical stimulation in animals and man. Of the thermal stimulation modalities, heat is the most commonly used, as a variety of reliable stimulation techniques are available. Heat is a natural stimulus modality to evoke pain, and it has been used to study animal nociception and human pain perception for (a) examining the mechanisms of tissue injury and sensitisation and (b) quantifying the therapeutic effects of pharmacological, physical, and psychological interventions. This paper summarises the current understanding of the physiology and psychophysical response to painful heat stimulation in humans. By understanding the underlying mechanisms, new methods of heat stimulation may be developed for basic and clinical applications. Traditionally, contact heat, indirect thermal heat by focused light bulb, and laser pulses have been the methods used to induce heat pain in humans for experimental and clinical studies. The following lasers have been used in pain research: argon (488-515 nm), copper vapour (510-577 nm), semiconductor (e.g. 970 nm), neodymium-YAG (1064 nm), thulium-YAG (2000 nm), and CO(2) (10,600 nm).

Hot Temperature↗

Assessment of nociceptive trigeminal pathways by laser-evoked potentials and laser silent periods in patients with painful temporomandibular disorders.

We assessed the trigeminal nociceptive pathways in patients with painful temporomandibular disorders (TMD) and control subjects using a CO(2)-laser stimulator which provides a predominant activation of the nociceptive system. Fifteen patients with unilateral pain were examined in accordance with the Research Diagnostic Criteria for TMD and 30 gender- and age-matched individuals were included as a control group. Laser-evoked potentials (LEPs) and laser silent periods (LSPs) after stimulation of the perioral region (V2/V3) on the painful and non-painful sides were recorded in all subjects. LEPs were evoked by low-intensity pulses (1.5 x perception threshold (PTh)) and recorded from scalp electrodes at the vertex. LSPs were evoked by high-intensity pulses (4 x PTh) and recorded bilaterally from masseter muscles with surface electromyogram (EMG) electrodes. Subjects also assessed the stimulus intensity on a 0-10 rating scale. LEPs had normal latency but smaller amplitude in TMD patients compared to the control group (P<0.001). Side-to-side comparison within patients showed that LEP amplitude was even more reduced after stimulation on the painful than the non-painful side (P<0.001). TMD patients showed a significant side-asymmetry of the pre-stimulus EMG activity, with a smaller value in the muscle on the painful side (P<0.001). LSPs were completely absent bilaterally in 12 TMD patients and unilaterally in two patients; only one patient had normal and bilateral LSPs. TMD patients perceived the laser stimulus less intense on the painful than the non-painful side (P<0.05). We found suppression of cortical responses and brainstem reflexes elicited by a predominantly nociceptive input in TMD patients. These findings are consistent with recent experimental pain studies and suggest that chronic craniofacial pain in TMD patients may be associated with a dysfunction of the trigeminal nociceptive system.

Adult↗

Spatial and temporal profiles of flare and hyperalgesia after intradermal capsaicin.

Intradermal injection of capsaicin induces a region of visual flare (neurogenic inflammation) and regions with modality specific hyperalgesia. Their temporal and spatial profiles have been studied to elucidate the mechanism behind neurogenic inflammation and hyperalgesia. Until today, the flare response has mainly been quantified by visual inspection. However, recent developments of thermography and laser-Doppler flowmetry have facilitated quantitative measurement of the neurogenic inflammation. The purpose of the present study was (1). to measure the temporal and spatial profiles of neurogenic inflammation and hyperalgesia induced by capsaicin by using thermography/laser-Doppler flowmetry and various sensory tests, and (2). to correlate the parameters related to neurogenic inflammation with the areas of secondary hyperalgesia. Eight healthy volunteers were injected intradermally with 250 microg of capsaicin. Five minutes after the injection, temperature and blood flow were measured by thermography and a laser-Doppler flowmetry, and followed by assessment of visual flare and hyperalgesia. Punctate hyperalgesia, stroking hyperalgesia, and heat hyperalgesia were assessed by von Frey hair, cotton swab, and radiant heat stimulator, respectively. This procedure was repeated 30 and 60 min after the injection. A significant increase in blood flow and temperature was detected by laser-Doppler flowmetry and thermography (F=102.08, P<0.001, and F=8.46, P=0.002, respectively). Throughout the experiment, the areas of visual flare, stroking hyperalgesia, and punctate hyperalgesia were covered by the area of significantly increased blood flow detected 5 min after the injection. The intensity of pain to heat stimuli significantly increased over time at the distal site and the proximal site (P<0.05). However, there was no significant difference between the pain intensity to radiant heat stimuli inside/outside the area of punctate hyperalgesia. These results seem to indicate that a possible contribution of neurogenic inflammation to secondary hyperalgesia (especially to radiant heat stimuli) must be reconsidered.

Capsaicin↗

Differential antinociceptive effects induced by a selective cyclooxygenase-2 inhibitor (SC-236) on dorsal horn neurons and spinal withdrawal reflexes in anesthetized spinal rats.

The aim of present study was to examine the effect of a selective cyclooxygenase-2 (COX-2) inhibitor SC-236 (4 mg/kg) on the simultaneous responsiveness of spinal wide-dynamic range (WDR) neurons and single motor units (SMUs) from gastrocnemius soleus muscles to mechanical stimuli (pressure and pinch) and repeated suprathreshold (1.5xT, the intensity threshold) electrical stimuli with different frequencies (3 Hz, 20 Hz) under normal conditions and bee venom (BV, 0.2 mg/50 microl)-induced inflammation and central sensitization. During normal conditions, the responses of SMUs, but not WDR neurons, to mechanical and repeated electrical stimuli (3 Hz, wind-up) were depressed by systemic administration of SC-236 as well as its vehicle (100% dimethyl sulfoxide (DMSO)). The after-discharges of both the WDR neurons and the simultaneously recorded SMUs after electrical stimuli with 20 Hz were markedly depressed only by SC-236, indicating that the mechanisms underlying the generation of the C-fiber mediated late responses and the after-discharges may be different. The enhanced responsiveness of both WDR neurons and SMUs to mechanical pressure stimuli (allodynia) and pinch stimuli (hyperalgesia) in the BV experiments was apparently depressed by SC-236, but not its vehicle. For electrical stimulation, the enhanced late responses and after-discharges, but not early responses, of both the WDR neurons and the simultaneously recorded SMUs were markedly depressed only by SC-236. This indicates that different central pharmacological mechanisms underlie the generation of these enhanced early, late responses, and after-discharges during BV-induced inflammation. The data suggest that the COX-2 inhibitor SC-236 apparently depress the activities of both spinal cord dorsal horn neuron and spinal withdrawal reflex during BV-induced sensitization, indicating that COX-2 plays an important role in the maintenance of central sensitization.

Action Potentials↗

Pharmacological modulation of experimental phasic and tonic muscle pain by morphine, alfentanil and ketamine in healthy volunteers.

BACKGROUND: Muscle pain is a major clinical problem but the underlying mechanisms and its pharmacological modulation need further investigation. This study on 15 volunteers evaluates if two experimental muscle pain models are sensitive to micro -receptor agonists and to an N-methyl-D-aspartate (NMDA)-receptor antagonist. METHODS: In the left tibialis anterior, intramuscular electrical (IMES) pain thresholds were determined for single (SPTmuscle) and five (RPTmuscle) repeated stimuli. Also pain to suprathreshold stimulation at 150% of RPTmuscle, 10 s, was assessed on a visual analog scale (VAS) as AUCimes (area under the VAS curve). In the right TA muscle, pain intensity on infusion of 0.5 ml of hypertonic saline, 5% (AUCsaline) and pain distribution indicated as local and referred were evaluated. Pain variables were assessed before, during and after intravenous infusions of morphine (10 microg x kg-1 min-1, 10 min), alfentanil (target-controlled infusion, plasma concentration; 60 ng ml-1, 60 min) and ketamine (10 microg x kg-1 min-1, 60 min). All data were normalized to baseline pain values (before drug infusions were initiated) and compared with placebo (midazolam, 2 microg x kg-1 min-1, 10 min). RESULTS: SPTmuscle increased (log mean values +/- SD, mA) with morphine (0.11 +/- 0.17, P < 0.05), alfentanil (0.28 +/- 0.24, P < 0.001) and ketamine (0.19 +/- 0.18, P < 0.01) as compared with placebo (-0.03 +/- 0.12). Alfentanil and ketamine also increased RPTmuscle (0.25 +/- 0.21, P < 0.01 and 0.21 +/- 0.19, P < 0.05, respectively) as compared with placebo (0.00 +/- 0.17). Pain to IMES (AUCimes) was reduced (median values [25th-75th percentiles], cm x s) by alfentanil and ketamine (-19.7 [-14.6 - -29.6] and-12.8 [-8.3 - -27.8], P < 0.05, respectively) vs. placebo (-0.8 [1.6 - -12.3]). Similar drug effects were seen when pain to infusion of hypertonic saline (AUCsaline) was assessed (alfentanil:-388 [-99 - -677] and ketamine:-326 [-227 - -573], P < 0.05 compared with placebo: 150 [449--240]). Ketamine also reduced the size of the local pain area (-58.4 [-21.2 - -176.1], < 0.05) as compared with placebo (-0.4 [70.6 - -13.4]). The frequency of referred pain was also lower when ketamine was given (3/13, P < 0.05) vs. placebo (9/14). CONCLUSION: The study demonstrates that experimental muscle pain induced in humans by electrical stimulation and infusion of hypertonic saline is sensitive to pharmacological modulation similar to preclinical animal tests and clinical trials. The data suggest that these models can be valuable tools in analgesic drug development.

Adult↗

Lumbar epidural fentanyl: segmental spread and effect on temporal summation and muscle pain.

BACKGROUND: Despite extensive use, different aspects of the pharmacological action of epidural fentanyl have not been clarified. We applied a multi-modal sensory test procedure to investigate the effect of epidural fentanyl on segmental spread, temporal summation (as a measure for short-lasting central hyperexcitability) and muscle pain. METHODS: Thirty patients received either placebo, 50 or 100 micro g single dose of fentanyl epidurally (L2-3), in a randomized, double-blind fashion. Heat pain tolerance thresholds at eight dermatomes from S1 to fifth cranial nerve (assessment of segmental spread), pain threshold to transcutaneous repeated electrical stimulation of the sural nerve (assessment of temporal summation) and pain intensity after injection of hypertonic saline into the tibialis anterior muscle (assessment of muscle pain) were recorded. RESULTS: Fentanyl 100 micro g, but not 50 micro g, produced analgesia to heat stimulation only at L2. Surprisingly, no effect at S1 was detected. Both fentanyl doses significantly increased temporal summation threshold and decreased muscle pain intensity. CONCLUSIONS: The findings suggest that a single lumbar epidural dose of fentanyl should be injected at the spinal interspace corresponding to the dermatomal site of pain. Increased effect on L2 compared with S1 suggests that drug effect on spinal nerve roots and binding to opioid receptors on the dorsal root ganglia may be more important than traditionally believed for the segmental effect of epidurally injected fentanyl. Epidural fentanyl increases temporal summation threshold and could therefore contribute to prevention and treatment of central hypersensitivity states. I.M. injection of hypertonic saline is a sensitive technique for detecting the analgesic action of epidural opioids.

Adult↗

Controlled mechanical distension of the human oesophagus: sensory and biomechanical findings.

BACKGROUND: The relation between mechanical distension of the gut and the sensory response is poorly understood. The current experimental study aimed to examine the sensory response in the human oesophagus during on-line recording of the luminal pressure, cross-sectional area (CSA) and sensory rating using different distension rates before and during relaxation of the smooth muscle. METHODS: An impedance planimetric probe for bag distension of the oesophagus was used in 13 healthy subjects aged 43 +/- 15 years. Ramp distensions were done with an electromechanical pump using infusion rates of 10, 25 and 50 ml/min, with and without relaxation of the smooth muscle with butylscopolamine. The sensory intensity was measured using a 0-10 visual analogue scale (VAS), with 5 as the pain threshold. The pump was reversed at 8 on the scale, corresponding to medium pain intensity, and the pressure, volume, tension and CSA were evaluated. Finally, three isovolumetric experiments where the CSA was held constant for 2 min at initial VAS ratings of 3, 5 and 7 were performed. RESULTS: A total of 104 distension profiles were investigated. The volume at maximal pain intensity (VAS = 8) increased as a function of the distension rate (P < 0.001), whereas the pressure, tension and CSA were not affected. When the smooth muscle was relaxed, there was a 29% fall in pressure at maximal pain intensity (P = 0.004), a 27% fall in tension (P = 0.003), whereas CSA did not change (P = 0.3). When the pressure was recorded as a function of the sensory intensity, there was an exponential increase after the pain threshold was reached, whereas the stimulus-response functions for tension, volume and CSA were nearly linear. In the isovolumetric experiments the ratings during the three sensory intensities were the same in the individual subjects, but the between-individual pain response was variable, probably reflecting individual differences in adaptation/central integration. CONCLUSIONS: The study allowed us to assess the strain-rate dependency of both perception and biomechanical properties in the oesophagus. It was demonstrated that the pain response was related to the CSA (and hence strain), independently of the contractile state of the muscle and biomechanical behaviour of the tissue. The findings support the fact that the pain-sensitive mechanoreceptors in the human oesophagus depend on circumferential wall stretch rather than on pressure, tension and volume. The model should be used in future studies to investigate whether changes in strain are responsible for the oesophageal sensation in health and disease.

Adult↗

Temporal summation of pain from skin, muscle and joint following nociceptive ultrasonic stimulation in humans.

This study investigated the phenomenon of temporal summation in response to repetitive focused ultrasound stimulation of skin, muscle and joint in human volunteers. Stimulation was carried out using a custom-designed, focused ultrasonic stimulator with a resonant frequency of 1.66 MHz. A series of stand-off attachments were used to ensure that the focal region of the ultrasound beam projected either cutaneously, within the distal interphalangeal joint of the index finger, or within the first dorsal interosseous muscle. Stimulation was carried out using single pulses and trains of five pulses of different pulse durations (25 ms, 50 ms, 75 ms, 100 ms), and using single pulses and trains of five pulses (50 ms duration) at different frequencies (0.5 Hz, 1 Hz, 2 Hz, 3 Hz, 4 Hz, 5 Hz). Tactile perception thresholds, pain thresholds and summation pain thresholds were recorded. Temporal summation of pain could be elicited by stimulation of both skin, joint and muscle, although the influence of temporal summation appeared to be more pronounced for muscle stimulation. Muscle stimulation also required greater ultrasound intensity compared with joint and skin stimulation. Temporal summation could not be elicited by tactile, low-intensity stimulation. Focused ultrasound is a potent, noninvasive technique with which to investigate temporal summation from somatic structures. A number of factors may account for the higher intensities required to elicit pain in muscle and the increased rate of temporal summation. It is clear, however, that if temporal summation is more pronounced in muscle than other tissues then this may be an important factor contributing to pain in musculoskeletal syndromes.

Adult↗

Thermosensitivity of muscle: high-intensity thermal stimulation of muscle tissue induces muscle pain in humans.

Small-calibre afferent units responding to thermal stimuli have previously been reported to exist in muscle. The question as to whether these receptors in humans mediate subjective thermal sensations from muscle remains unresolved. The aims of the present study were to determine in humans whether intramuscular injection of warm and cold isotonic saline elicits temperature sensations, muscle pain or any other sensations. In 15 subjects, no thermal sensations assessed on a temperature visual analogue scale (VAS) could be detected with intramuscular injections of isotonic saline (1.5 ml) into the anterior tibial muscle at temperatures ranging from 8 to 48 degrees C. The same subjects recorded strongly increasing scores on a temperature VAS when thermal stimuli in the same intensity range were applied to the skin overlying the muscle by a contact thermode. However, I.M. isotonic saline of 48 degrees C induced muscle pain with peak scores of 3.2 +/- 0.8 cm on a VAS scale ranging from 0 to 10 cm. Using the the McGill pain questionnaire a subgroup, of subjects qualitatively described the pain using the 'thermal hot' and 'dullness' word groups. Temperature measurements within the muscle during the stimulating injections showed that the time course of the pain sensation elicited by saline at 48 degrees C paralleled that of the intramuscular temperature and far outlasted the injection time. The present data show that high-intensity thermal stimulation of muscle is associated with muscle pain. High-threshold warm-sensitive receptors may mediate the pain following activation by temperatures of 48 degrees C or more. Taken together, the data indicate that thermosensation from a given volume of muscle is less potent than nociception.

Adult↗

Glutamate-induced sensitization of rat masseter muscle fibers.

In rats, intradermal or intraarticular injection of glutamate or selective excitatory amino acid receptor agonists acting at peripheral excitatory amino acid receptors can decrease the intensity of mechanical stimulation required to evoke nocifensive behaviors, an indication of hyperalgesia. Since excitatory amino acid receptors have been found on the terminal ends of cutaneous primary afferent fibers, it has been suggested that increased tissue glutamate levels may have a direct sensitizing effect on primary afferent fibers, in particular skin nociceptors. However, less is known about the effects of glutamate on deep tissue afferent fibers. In the present study, a series of experiments were undertaken to investigate the effect of intramuscular injection of glutamate on the excitability and mechanical threshold of masseter muscle afferent fibers in anesthetized rats of both sexes. Injection of 1.0 M, but not 0.1 M glutamate evoked masseter muscle afferent activity that was significantly greater than that evoked by isotonic saline. The mechanical threshold of masseter muscle afferent fibers, which was assessed with a Von Frey hair, was reduced by approximately 50% for a period of 30 min after injection of 1.0 M glutamate, but was unaffected by injections of 0.1 M glutamate or isotonic saline. Injection of 25% dextrose, which has the same osmotic strength as 1.0 M glutamate, did not evoke significant activity in or decrease the mechanical threshold of masseter muscle afferent fibers. Magnetic resonance imaging experiments confirmed that injection of 25% dextrose and 1.0 M glutamate produced similar edema volumes in the masseter muscle tissue. Co-injection of 0.1 M kynurenate, an excitatory amino acid receptor antagonist, and 1.0 M glutamate attenuated glutamate-evoked afferent activity and prevented glutamate-induced mechanical sensitization. When male and female rats were compared, no difference in the baseline mechanical threshold or in the magnitude of glutamate-induced mechanical sensitization of masseter muscle afferent fibers was observed; however, the afferent fiber activity evoked by injection of 1.0 M glutamate into the masseter muscle was greater in female rats. The results of the present experiments show that intramuscular injection of 1.0 M glutamate excites and sensitizes rat masseter muscle afferent fibers through activation of peripheral excitatory amino acid receptors and that glutamate-evoked afferent fiber activity, but not sensitization, is greater in female than male rats.

Action Potentials↗