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Capsaicin-induced Muscle Pain Alters the Excitability of the Human Jaw-stretch Reflex

¹ Center for Sensory-Motor Interaction, Orofacial Pain Laboratory, Aalborg University, Fredrik Bajers Vej 7 D-3, DK-9220 Aalborg S, Denmark;
² Department of Clinical Oral Physiology, Royal Dental College, University of Aarhus; and
³ Department of Maxillofacial Surgery, Aarhus University Hospital, Denmark;

* corresponding author, kelun{at}smi.auc.dk

	ABSTRACT

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The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw-stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 µg) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings.

KEY WORDS: stretch reflex • jaw-muscle pain • capsaicin • trigeminal physiology • human

	INTRODUCTION

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The jaw-stretch reflex has been investigated in patients with painful temporomandibular disorders (TMD) (Murray and Klineberg, 1984; Cruccu et al., 1997) and during experimental muscle pain conditions (Wang et al., 2000). Recent studies have indicated that intramuscular injection of capsaicin is a valuable technique for specific activation of human nociceptive groups III and IV muscle afferents (Marchettini et al., 1996), and has been used as an experimental model of craniofacial pain and hyperalgesia (Arima et al., 2000). Evidence from animal studies suggest that activation of groups III and IV muscle afferents can lead to increased fusimotor firing and increased sensitivity of the Ia muscle spindle afferents to stretch (Johansson et al., 1993; Pedersen et al., 1997; Hellström et al., 2000; Thunberg et al., 2002). This could be seen as a facilitation of the short-latency stretch reflex during ongoing pain. Recent human studies have, indeed, shown that experimental pain evoked by intramuscular injection of hypertonic saline is associated with increases in the amplitude of the stretch reflex (Matre et al., 1998, 1999; Wang et al., 2000). However, hypertonic saline could also activate non-nociceptive afferents. Therefore, capsaicin was chosen in the present study to evoke jaw-muscle pain.

The amplitude of the jaw-stretch reflex is influenced by the velocity and displacement of the stretch (Lobbezoo et al., 1993; Poliakov and Miles, 1994). Consistent with these results, the amplitude of the jaw-stretch reflex has been shown to increase proportionally with increasing stretch displacement at a given ramp time, and to increase proportionally with increasing stretch velocity at a given displacement (Wang and Svensson, 2001). The length sensitivity is mainly adjusted by the static fusimotor system, whereas the velocity sensitivity is under the control of the dynamic fusimotor system (Matthews, 1972). The relationship between stretch velocity and stretch amplitude (input-output curve) can be used to study the gain of the system. For example, steeper slopes of the input-output curves represent an increased gain, which could be due to an increased activity of the dynamic fusimotor system (Nielsen et al., 1998). The pain-related facilitation of the stretch reflex in the soleus and tibialis muscles could be explained by an increase in the dynamic rather than the static fusimotor system (Matre et al., 1998). However, a predominant activation of static fusimotor neurons following intramuscular injection of hypertonic saline in cats has recently been observed (Thunberg et al., 2002). Thus, the influence of experimental muscle pain on the length and velocity sensitivity of the jaw-stretch reflex needs further investigation.

The aims of the present study were to test the hypothesis that specific activation of nociceptive muscle afferent fibers in human is linked to an increase in the excitability of the jaw-stretch reflex and to determine the influence of length (displacement) and velocity of the stretch on this process.

	MATERIALS & METHODS

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Eleven healthy volunteers, ten men and one woman (mean age ± SEM: 25.3 ± 0.9 yrs), participated in this experiment. The study was conducted in accordance with the Helsinki Declaration, and informed consent was obtained from all subjects. The local ethics committee approved the study.

Experimental Protocol
Stretch reflexes were evoked in the jaw-closing muscles with the use of a standardized stretch device (Miles et al., 1993; Wang et al., 2000). The subjects were instructed to bite on the jaw-bar with their incisors during the recordings. The initial jaw separation for the subjects was determined by the distance between the upper and lower jaw-bars, which was 4.0 mm in all experiments.

In the first part of the experiment, 10 different ramp times were used (10, 20, 40, 60, 80, 100, 150, 200, 250, and 300 msec) in combination with a constant displacement of the stretch (1 mm). The stretch velocities were therefore 100, 50, 25, 16.7, 12.5, 10, 6.7, 5, 4, and 3.3 mm/sec. Twelve sweeps were recorded at each velocity with at least a five-second interval between each sweep. The different velocities were tested in random order. In the second part of the experiment, five displacements (0.25, 0.5, 1.0, 1.5, and 2.0 mm) were tested in random order. The velocity was kept constant at 25 mm/sec by adjustment of the ramp times (10, 20, 40, 60, and 80 msec, respectively).

Experimental Muscle Pain
Injection of capsaicin (0.1 mL, 100 µg/mL) was used in this study to evoke pain in the masseter muscle. The bolus injection was administered into the posterior part of the right masseter muscle about 2 cm from the surface electromyographic (EMG) electrodes. The total duration of the manual injection was about 5 sec. The subjects continuously scored the pain intensity on a 10-cm electronic visual analogue scale (VAS), with the lower extreme marked "no pain" and the upper extreme marked "most pain imaginable". The mean VAS score was calculated starting at the same time as the stretch reflex recordings. After the end of the pain, the subjects described the quality of pain on a Danish version of the McGill Pain Questionnaire.

Reflex Recordings
The EMG activity was recorded bilaterally with the use of bipolar disposable surface electrodes (4 x 7 mm recording area, 720-01-k; Neuroline, Medicotest, Ølstykke, Denmark) placed 10 mm apart along the central part of the masseter and the anterior temporalis muscles. The skin over the recording positions was cleaned with alcohol. A ground electrode soaked with saline was attached to the subject’s right wrist. The EMG signals were amplified 2000-5000 times (Counterpoint MK2, Skovlund, Denmark), bandpass-filtered (from 20 Hz to 1 kHz), sampled at 4 kHz, and stored for off-line analysis (Wang et al., 2000).

The subjects were first asked to perform 3 maximal clenches, each lasting up to 3 sec, on the jaw-bar with their incisor teeth to obtain the mean EMG value of the maximal voluntary contraction (MVC) in the 4 muscles. During the experiment, the subjects were asked to maintain the EMG at 10% MVC, guided by visual feedback from the right masseter muscle. Recordings of jaw-stretch reflexes were obtained during 3 experimental conditions: before, during, and 15 min after the pain had vanished. A computer program automatically triggered the jaw-muscle stretcher when the EMG activity remained within the pre-set window for more than 400 msec. A total of 300 msec of EMG activity was recorded, with 100 msec pre-stimulus and 200 msec post-stimulus.

Analysis
The mean of the rectified EMG in the pre-stimulus interval (from -100 to 0 msec) was calculated (Lobbezoo et al., 1993). The peak-to-peak amplitude of the short-latency (from 8 to 10 msec) reflex component, which appeared as a biphasic potential in the average of the non-rectified recordings, was measured in the different experimental conditions. The peak-to-peak amplitude was then normalized with respect to the mean pre-stimulus EMG activity (Fig. 1).

View larger version (10K): [in this window] [in a new window]   Figure 1. Averaged reflex response (12 sweeps) in the right masseter evoked by fast stretch (ramp time: 10 ms) in a single subject. Arrow shows the onset of the stretch stimulus. The amplitude was measured as the peak-to-peak value. The normalized peak-to-peak amplitude was calculated as the pre-stimulus EMG divided by peak-to-peak amplitude.

	RESULTS

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Experimental Muscle Pain
All eleven subjects perceived the capsaicin injection into the right masseter as painful. The mean VAS score during stretch reflex recordings was 6.8 ± 0.5 cm. The pain was focused in the right masseter and spread toward the temporomandibular joint and temple (5/11) and the upper or lower right molar teeth (3/11). All subjects reported no pain (VAS = 0) 20 min after the injection. However, a slight soreness usually persisted during the last recording.

Influence of Stretch Velocity
Two-way ANOVAs of the normalized peak-to-peak amplitude of the jaw-stretch reflex demonstrated a significant effect of velocity in all 4 muscles (two-way ANOVA: F > 6.71, P < 0.001) and a significant effect of experimental condition (two-way ANOVA: F > 3.83, P < 0.039). There was a significant interaction between the stretch velocity and the experimental condition in the right masseter and temporalis muscles (P < 0.01). The post hoc analysis showed significant increases in the peak-to-peak amplitudes during muscle pain as compared with pre- and post-pain conditions at velocities of 25, 50, and 100 mm/sec for the right masseter muscle, and at 100 mm/sec for the right temporalis muscle (P < 0.05) (Figs. 2B, 2D).

View larger version (17K): [in this window] [in a new window]   Figure 2. Normalized peak-to-peak amplitude of stretch reflexes in left (A) and right (B) masseter and left (C) and right (D) temporalis muscles evoked at different stretch velocities and the effect of injection of capsaicin into the right masseter. The ordinate axis represents the percentage of normalized peak-to-peak amplitude. For clarity, the stretch velocity is displayed on a logarithmic scale. Mean values + SEM (n = 11). * indicates significant difference between conditions (SNK: P < 0.05).

Influence of Stretch Displacement
Five different stretch displacements were investigated with different ramp times to keep the velocity constant. There was no significant effect of the stretch displacement on the normalized peak-to-peak amplitude in the 4 muscles (two-way ANOVA: F < 1.18, P > 0.36) (Figs. 3A-3D). Two-way ANOVAs indicated significantly higher values during the pain conditions compared with pre- and post-pain conditions in the right masseter muscle (F = 6.39, P = 0.007), with no interaction between conditions and displacements (two-way ANOVA: F = 0.69, P = 0.70) (Fig. 3B).

View larger version (20K): [in this window] [in a new window]   Figure 3. Normalized peak-to-peak amplitude of stretch reflexes in left (A) and right (B) masseter and left (C) and right (D) temporalis muscles evoked at different displacements. Note: The stretch velocity of 25 mm/sec is constant, since the ramp time is adjusted accordingly. Mean values + SEM (n = 11). Two-way ANOVAs indicated significantly higher amplitudes during the pain condition compared with the pre- and post-pain conditions in the right masseter.

	DISCUSSION

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The amplitude of the jaw-stretch reflex has been shown to increase proportionally with increasing stretch displacement at a given ramp time (Wang and Svensson, 2001). When the stretch velocity was kept constant by changing the ramp time corresponding to the different displacements in this study, there was no significant effect of stretch displacement (Figs. 3A-3D). The reflex amplitude increased proportionally with increasing velocity at a fixed displacement (Figs. 2A-2D). These findings strongly suggest that the sensitivity of the jaw-stretch reflex is mainly dependent on the velocity of the stretch and not on the displacement.

The amplitude of the jaw-stretch reflex can be influenced by the descending drive from higher centers through cortico-trigeminal projections, pre-synaptic modulation of afferent inputs to the motoneuron pool, and by the level of fusimotor activity. In the present study, when the overall level of the pre-stimulus EMG was kept constant, the facilitation of jaw-stretch reflex was most prominent on the painful side, with significant increases in the masseter and anterior temporalis muscles (Figs. 2B, 2D). However, in accordance with our previous studies (Svensson et al., 2000, 2001; Wang et al., 2000), a tendency of bilateral facilitation was also observed (Figs. 2A, 3A). It appears that the contralateral effects in humans are less pronounced and more variable compared with the ipsilateral effects of pain which could be related to the bilateral, but not symmetrical, cortico-trigeminal projections during voluntary contraction of the jaw-closing muscles (Nordstrom et al., 1999), in addition to a larger sweep-to-sweep variability of pre-stimulus EMG activity in the non-feedback muscles (Svensson et al., 2001).

It is also possible that activation of nociceptive afferents could change the pre-synaptic modulation of the Ia afferent input to the motoneuron pool to explain the facilitation of the jaw-stretch reflex. However, there is no direct evidence to support this hypothesis, and H-reflex studies have consistently failed to demonstrate facilitation of the motoneuron pool during ongoing experimental muscle pain (Matre et al., 1998; Svensson et al., 1998). In fact, H-reflexes may instead be depressed following deep nociceptive inputs (Rossi and Decchi, 1997; Le Pera et al., 2001).

A series of animal studies has demonstrated that various algogenic substances, including hypertonic saline, can induce statistically significant changes in muscle spindle afferent activity (e.g., Jonhansson et al., 1993; Pedersen et al., 1997; Thunberg et al., 2002). Thus, a predominant effect on static fusimotor neurons was noted in 64 out of 84 responses, and it was suggested that the changes in muscle spindle afferent activity were most likely mediated via fusimotor reflexes (Thunberg et al., 2002). However, responses indicative of mixed static and dynamic fusimotor activity were also observed (16/84 responses) (Thunberg et al., 2002). In accordance, intramuscular injection of hypertonic saline in cats consistently modulates static neurons (100% of tested cells) located in the medial edge of the nucleus interpolaris, whereas neurons with dynamic-static properties are modulated less often (69% of tested cells) (Capra and Ro, 2000). These authors have suggested that the hypertonic saline-induced changes in the proprioceptive properties of brainstem neurons are in accordance with the notion that muscle nociceptors acting through interneurons alter fusimotor drive, which in turn alters muscle spindle primary and secondary endings (Capra and Ro, 2000; Ro and Capra, 2001). The present findings in humans—that the slope of the input-output curve was increased during ongoing jaw-muscle pain—also support the notion that the dynamic fusimotor system could play a role in a pain-related perturbation of jaw-motor function. However, further animal and human studies will be needed to understand the functional implications of these changes, i.e., how the awareness of the dynamic and static aspects of the position and movements of the jaw is influenced by muscle pain.

In conclusion, the present results indicated that the jaw-stretch reflex was more sensitive to stretch velocity than to displacement. Furthermore, the results suggested that inputs from thin nociceptive afferents can increase the sensitivity of the fusimotor system.

	ACKNOWLEDGMENTS

 
The Danish National Research Foundation and the Danish Dental Association supported the present study. The comments from Dr. Ken Yoshida are greatly appreciated.

Received October 15, 2001; Last revision June 14, 2002; Accepted July 8, 2002

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS RESULTS DISCUSSION REFERENCES

 
Arima T, Svensson P, Arendt-Nielsen L (2000). Capsaicin-induced muscle hyperalgesia in the exercised and non-exercised human masseter muscle. J Orofac Pain 14:213–223.[Medline]

Capra NF, Ro JY (2000). Experimental muscle pain produces central modulation of proprioceptive signals arising from jaw muscle spindles. Pain 86:156–162.

Cruccu G, Frisardi G, Pauletti G, Romaniello A, Manfredi M (1997). Excitability of the central masticatory pathways in patients with painful temporomandibular disorders. Pain 73:447–454.[Medline]

Hellström F, Thunberg J, Bergenheim M, Sjölander P, Pedersen J, Johansson H (2000). Elevated intramuscular concentration of bradykinin in jaw muscle increases the fusimotor drive to neck muscles in the cat. J Dent Res 79:1815–1822.[Abstract/Free Full Text]

Johansson H, Djupsjöbacka M, Sjölander P (1993). Influences on the gamma-muscle spindle system from muscle afferents stimulated by KCl and lactic acid. Neurosci Res 16:49–57.[Medline]

Le Pera D, Graven-Nielsen T, Valeriani M, Oliviero A, Di Lazzaro V, Tonali PA, et al. (2001). Inhibition of motor system excitability at cortical and spinal level by tonic muscle pain. Clin Neurophysiol 112:1633–1641.[Medline]

Lobbezoo F, van der Glas HW, Buchner R, van der Bilt A, Bosman F (1993). Gain and threshold of the jaw-jerk reflex in man during isometric contraction. Exp Brain Res 93:129–138.[Medline]

Marchettini P, Simone DA, Caputi G, Ochoa JL (1996). Pain from excitation of identified muscle nociceptors in humans. Brain Res 740:109–116.[Medline]

Matre DA, Sinkjaer T, Svensson P, Arendt-Nielsen L (1998). Experimental muscle pain increases the human stretch reflex. Pain 75:331–339.[Medline]

Matre DA, Sinkjaer T, Knardahl S, Andersen JB, Arendt-Nielsen L (1999). The influence of experimental muscle pain on the human soleus stretch reflex during sitting and walking. Clin Neurophysiol 110:2033–2043.[Medline]

Matthews PBC (1972). Mammalian muscle receptors and their central actions. London: Arnold.

Miles TS, Poliakov AV, Flavel SC (1993). An apparatus for controlled stretch of human jaw-closing muscles. J Neurosci Meth 46:197–202.[Medline]

Murray GM, Klineberg IJ (1984). Electromyographic recordings of human jaw-jerk reflex characteristics evoked under standardized conditions. Arch Oral Biol 29:537–549.[Medline]

Nielsen JF, Andersen JB, Barbeau H, Sinkjaer T (1998). Input-output properties of the soleus stretch reflex in spastic stroke patients and healthy subjects during walking. NeuroRehabilitation 10:151–166.

Nordstrom MA, Miles TS, Gooden BR, Butler SL, Ridding MC, Thompson PD (1999). Motor cortical control of human masticatory muscles. Prog Brain Res 123:203–214.[Medline]

Pedersen J, Sjölander P, Wenngren BI, Johansson H (1997). Increased intramuscular concentration of bradykinin increases the static fusimotor drive to muscle spindles in neck muscles of the cat. Pain 70:83–91.[Medline]

Poliakov AV, Miles TS (1994). Stretch reflexes in human masseter. J Physiol 476:323–331.[Abstract/Free Full Text]

Ro JY, Capra NF (2001). Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline. Pain 92:117–127.[Medline]

Rossi A, Decchi B (1997). Changes in Ib heteronymous inhibition to soleus motoneurones during cutaneous and muscle nociceptive stimulation in humans. Brain Res 774:55–61.[Medline]

Svensson P, De Laat A, Graven-Nielsen T, Arendt-Nielsen L (1998). Experimental jaw-muscle pain does not change heteronymous H-reflexes in the human temporalis muscle. Exp Brain Res 121:311–318.[Medline]

Svensson P, Miles TS, Graven-Nielsen T, Arendt-Nielsen L (2000). Modulation of stretch-evoked reflexes in single motor units in human masseter muscle by experimental pain. Exp Brain Res 132:65–71.[Medline]

Svensson P, Macaluso GM, De Laat A, Wang K (2001). Effects of local and remote muscle pain on human jaw reflexes evoked by fast stretches at different clenching levels. Exp Brain Res 139:495–502.[Medline]

Thunberg J, Ljubisavljevic M, Djupsjöbacka M, Johansson H (2002). Effects on the fusimotor-muscle spindle system induced by intramuscular injections of hypertonic saline. Exp Brain Res 142:319–326.[Medline]

Wang K, Svensson P (2001). Influence of methodological parameters on human jaw-stretch reflexes. Eur J Oral Sci 109:86–94.[Medline]

Wang K, Svensson P, Arendt-Nielsen L (2000). Effect of tonic muscle pain on short latency jaw-stretch reflexes in humans. Pain 88:189–197.[Medline]

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