&p.1:Abstract The effects of bilateral experimental musclepain on human masticatory patterns were studied. Jawmovements and electromyographic (EMG) recordings ofthe jaw-closing muscles were divided into multiple sin-gle masticatory cycles and analyzed on a cycle-by-cyclebasis. In ten men simultaneous bilateral injections of hy-pertonic saline (5%) into the masseter muscles causedstrong pain (mean±SE: 7.5±0.4 on a 0–10 scale), signifi-cantly reduced EMG activity of jaw-closing muscles inthe agonist phase, and significantly increased EMG ac-tivity in the antagonist phase. Nine of the subjects report-ed a sensation of less intense mastication during pain. In-jections of isotonic saline (0.9%) did not cause pain orsignificant changes in masticatory patterns. The influ-ence of higher brain centers on conscious human masti-cation can not be discarded but the observed phase-de-pendent modulation could be controlled by local neuralcircuits and/or a central pattern generator in the brainstem which are capable of integrating bilateral nocicep-tive afferent activity.

&kwd:Key words Experimental muscle pain · Mastication ·Central pattern generator&bdy:

Introduction

Mastication is based on complex interactions betweenneural activity in the cortical masticatory area and the lat-eral region of the face motor cortex, the corticobulbartract, local circuits in the brain stem and peripheral affer-ent input (Luschei and Goldberg 1981; Lund and Enomoto1988; Sessle et al. 1995). Distinct populations of premotorneurons within the brain stem constitute a central pattern

generator (CPG) that is implicated in rhythm and burstgeneration and integration of afferent information (Dellowand Lund 1971; Olsson et al. 1986; Lund 1991). Nocicep-tive afferent activity may via this CPG or interneurons fa-cilitate inhibitory pathways to jaw-closing motorneuronsin the agonist phase and facilitate excitatory pathways inthe antagonist phase (Lund et al. 1991, 1993). In accor-dance with this suggestion, reduced electromyographic(EMG) activity of jaw-closing muscles in the agonistphase has been observed during experimental painful mas-tication in both humans and animals (Schwartz and Lund1995; Svensson et al. 1996). Studies in animals have fur-thermore shown that deep noxious stimulation can causeincreased EMG activity of jaw-closing and jaw-openingmuscles during resting conditions (Yu et al. 1995, 1996)and increased EMG activity of jaw-closing muscles in theantagonist phase during mastication (Schwartz and Lund1995). The experimental human studies have so far stud-ied the motor effects of unilateral muscle pain (Lund et al.1991; Svensson et al. 1996); however, clinical jaw musclepain is often bilateral (Reid et al. 1994). It is not knownwhether unilateral and bilateral muscle pain cause differ-ential effects on human deliberate mastication. The aim ofthis study was to induce intense bilateral muscle pain anddescribe the effects on masticatory patterns on a cycle-by-cycle basis to account for variability between cycles. Fur-thermore, non-painful injections of isotonic saline wereincluded in the present study as controls.

Materials and methods

Ten healthy men (mean age 23.6±0.9 years) were included in thestudy. The absence of temporomandibular disorders was verifiedby standard screening procedures (American Academy of Orofa-cial Pain 1996). Informed consent according to the Helsinki-IIDeclaration was obtained from all subjects prior to study entry.The study had been approved by the local ethics committee.

Jaw movements and electromyography

A Sirognathograph (Siemens, Germany) was used to track jawmovements at the lower incisors in three dimensions (Lewin 1985;

P. SvenssonDepartment of Prosthetic Dentistry, Aarhus University, Aarhus, Denmark

P. Svensson (✉) · L. Houe · L. Arendt-NielsenCenter for Sensory-Motor Interaction, Aalborg University, Fredrik Bajersvej 7 D-3, DK-9220 Aalborg, DenmarkFax: +45 9815 4008, e-mail: psv@miba.auc.dk&/fn-block:

Exp Brain Res (1997) 116:182–185 © Springer-Verlag 1997

R E S E A R C H N OT E

&roles:Peter Svensson · Lars Houe · Lars Arendt-Nielsen

Bilateral experimental muscle pain changes electromyographic activity of human jaw-closing muscles during mastication

&misc:Received: 19 February 1997 / Accepted: 14 April 1997

183

Svensson et al. 1996). Bipolar surface silver electrodes (12×6 mm)were placed 10 mm apart along the central part of the massetermuscles and the anterior temporalis muscles. The EMG signalswere amplified differentially (5000–20 000 times; Disa 15C01,Denmark), filtered (20–500 Hz), sampled at 1024 Hz, and storedtogether with the electrognathographic (EGG) signals. Subjectschewed one piece of gum (1.5 g, Sorbits) with three orthodonticelastics (Energy Pak Elastics, 280, USA) on their preferred chew-ing side in their own rhythm. EGG and EMG signals during gum-chewing were sampled for 30 s before, during and 10 min after ex-perimental bilateral pain had been induced in the masseter muscles.Sterile hypertonic saline (5%, 0.2 ml) was injected over 15 s intothe mid-portion of the left and right masseter muscles (Svensson etal. 1996). On a separate day 0.2 ml isotonic saline (0.9%) was in-jected into the masseter muscle on one side and the effect on masti-catory patterns was examined. The sequence of hypertonic and iso-tonic injections was randomized in a balanced manner. The pain in-tensity was rated by the subjects on a 10-cm visual analog scalewhere the left extreme denoted “no pain” and the right extreme“worst imaginable pain”.The EGG signals were linearized and fil-tered by a low-pass finite impulse response filter (filter order=20,cutoff frequency=10 Hz). The differentiated vertical position was

used to determine the onset of the jaw-opening phase, which wasdefined as the zero-crossing velocity where the velocity changedfrom positive (jaw-closing) to negative (jaw-opening). Onset wasmarked when the velocity in a moving 20-sample window wasabove a defined threshold of 10 mm/s (Svensson et al. 1996). Theonset of the closing phase was determined as the highest EGG val-ue (negative) during jaw-opening. The period from the start of onejaw-opening phase to the next jaw-opening phase was defined as amasticatory cycle. For jaw-closing muscles, the jaw-opening phasecorresponds to the antagonist phase and the jaw-closing phase tothe agonist phase. The EMG and EGG signals were divided intomultiple single masticatory cycles which were analyzed on a cycle-by-cycle basis. Since the subjects were instructed to avoid swallow-ing, a small number of masticatory cycles had to be discarded inthe analysis. For each accepted masticatory cycle the maximal dis-placement of the jaw movement (mm) was calculated in addition tothe duration (ms) and the root-mean-square (RMS) value (µV) ofthe rectified EMG activity in the jaw-opening (antagonist) and jaw-closing (agonist) phase. A total of 25 consecutive cycles were ana-lyzed for hypertonic saline and 23 cycles for isotonic saline.

MANOVAs with repeated measures were used to analyze theeffect of the factors: subjects (10), experimental condition (3: pre-

Fig. 1 Effect of bilateral injec-tion of hypertonic saline onmean electromyographic(EMG) activity of all jaw-clos-ing muscles measured as root-mean-square (RMS) values inthe agonist and antagonistphase. Bottom panelshows themaximal vertical displacementof the mandible during masti-cation. A total of 25 consecu-tive masticatory cycles was an-alyzed. Plus signindicate thatthe painful condition (during)is significantly different fromboth the before-pain conditionand the after-pain condition(SNK: P<0.05)&/fig.c:

184

pain, pain, post-pain), masticatory cycle (25 and 23), muscle re-cording site (4: masseter and anterior temporalis muscles). Student-Newman-Keuls (SNK) post-hoc tests were used to compensate formultiple comparisons. Significance was accepted at P<5%.

Results

Injection of isotonic saline into the masseter muscle wasassociated with no or very low pain scores (0.4±0.1)whereas bilateral injections of hypertonic saline causedstrong pain (7.5±0.4). Nine subjects reported a sensation ofless intense mastication during pain.For bilateral injectionsof hypertonic saline there were no significant main effectsof experimental condition, but MANOVA analyses of theEMG activity in the jaw-closing and jaw-opening phase re-vealed a highly significant interaction between experimen-tal condition and masticatory cycles [F(48,5472)=5.77,P<0.0001; F(48,5472)=2.16, P<0.0001]. During painfulmastication the mean EMG activity of all the jaw-closingmuscles in the agonist phase was significantly decreased(SNK: P<0.05) and the mean EMG activity of all the jaw-closing muscles in the antagonist phase was significantlyincreased as compared with painfree mastication (pre-painand post-pain) (SNK: P<0.05) (Fig. 1). An example of re-duced EMG agonist bursts in the masseter muscle on thechewing side (ipsilateral) is shown in Fig. 2, but the statis-tical analysis did not separate out an effect of pain on spe-cific muscles. We found no significant effects of bilateralinjections on the maximal displacements (Fig. 1) or on theduration of the jaw-opening and jaw-closing phase even

though some subjects showed a reduction in the verticaldisplacement (Fig. 2). A complete preservation or evenslight increase of the masticatory rhythm during pain canalso be seen in Fig. 2. Injection of isotonic saline caused nosignificant changes in EMG activity or jaw movements.

Discussion

A consistent effect of experimental pain on mastication inboth conscious humans and decerebrated animals is a re-duction of the jaw-closing EMG activity in the agonistphase (Schwartz and Lund 1995; Svensson et al. 1996).This was confirmed in the present study with analysis ofmultiple masticatory cycles and bilateral pain. The reduc-tion of agonist EMG activity seems to be specific to painbecause injection of isotonic saline did not cause any sig-nificant changes. With intense bilateral pain we now ob-served a significant increase in EMG activity of jaw-clos-ing muscles in the antagonist phase. This finding suggeststhat a small co-contraction of the jaw-closing muscles oc-curs at high levels of experimental pain and/or with wideopening of the jaws (Stohler et al. 1990). Noxious stimu-lation of the temporomandibular joint and deep paraspi-nal tissues in rats has previously been shown to cause in-creased EMG activity of both jaw-closing and jaw-open-ing muscles during resting conditions (Hu et al. 1993; Yuet al. 1995, 1996). Co-contraction of jaw muscles duringmastication has also been described in patients with pain-ful temporomandibular disorders (Møller et al. 1984;

Fig. 2 Masticatory activity inone subject before and duringpain. Lower trace: EMG re-cordings of the masseter mus-cle ipsilateral (il-mas) to thebolus. Upper trace: Note in thissubject the reduced amplitudeof jaw movements (Z) and theslight increase in masticatoryrhythm during painful mastica-tion&/fig.c:

185

Stohler et al. 1988) and could be interpreted as an effectof pain rather than a cause of pain.Obviously, experi-ments in decerebrated animals differ from human masti-cation studies in several ways. First, human masticationon a bolus requires additional muscle activity beyond theactivity necessary for rhythmical empty open-close move-ments (Dubner et al. 1978; Ottenhoff et al. 1993). Thisdifference in both efferent and afferent activity may alsocause differences in the nociceptive modulation of jawmotor function. Second, animal preparations which ex-clude the influence of cortical control mechanisms haveshown that brain stem structures can integrate nociceptiveafferent activity and modulate jaw motor function but it isdifficult in conscious humans to discard the influence ofhigher nervous centers (Sessle et al. 1995). Murray et al.(1991) and Lin et al. (1993) showed the importance of theface primary somatosensory cortex and face motor cortexfor the fine control of mastication and other orofacial mo-tor tasks in conscious monkeys. The fine control of hu-man mastication during painful muscle stimulation couldalso be affected by central loops. Third, the masticatorycycle in decerebrated rabbits is significantly increasedduring noxious stimulation (Schwartz and Lund 1995)whereas the masticatory cycle was unchanged in the pres-ent study. The lack of significant changes in human mas-ticatory rhythm combined with the consistent reduction inEMG bursts during agonist action could indicate that lo-cal circuits in the brain stem related to burst generationmay be relatively more responsive to nociceptive modula-tion than neurons related to rhythm generation. Westberget al. (1995) have recently shown that the firing patternsof premotor neurons are influenced by the form of the in-duced central rhythm. Thus, the same premotor neuronsmay be unresponsive during one movement pattern, pha-sically responsive during another and unchanged during athird. This supports our suggestion that nociceptive mod-ulation of human conscious mastication is similar, but notidentical to nociceptive modulation of rhythmic jaw mo-tor function in decerebrated animals because motor tem-plates and influence from higher brain centers are differ-ent.

In conclusion, we have with bilateral experimental mas-seter pain in humans shown a phase-dependent modulationof EMG activity in jaw-closing muscles during mastica-tion. This acute adjustment of jaw motor function was notobserved in control experiments with injections of isotonicsaline and suggests that bilateral nociceptive afferent activ-ity is effectively integrated by motor control circuits.

&p.2:Acknowledgements The study was supported by the DanishDental Association’s FUT and Calcin Foundation, Colgate-Palm-olive, and the Danish National Research Foundation.

References

American Academy of Orofacial Pain (1996) In: Okeson JP (ed)Orofacial pain: guidelines for assessment, diagnosis, and man-agement. Quintessence, Chicago

Dellow PG, Lund JP (1971) Evidence for central timing of rhyth-mical mastication. J Physiol 215: 1–13

Dubner R, Sessle BJ, Storey A (1978) The neural basis of oral andfacial function. Plenum Press, New York

Hu JW, Yu X-M, Vernon H, Sessle BJ (1993) Excitatory effects onneck and jaw muscle activity of inflammatory irritant appliedto cervical paraspinal tissues. Pain 55: 243–250

Lewin A (1985) Electrognathographics: atlas of diagnostic proce-dures and interpretation. Quintessence, Chicago

Lin L-D, Murray GM, Sessle BJ (1993) The effect of bilateralcold block of the primate face primary somatosensory cortexon the performance of trained tongue-protrusion task and bit-ing tasks. J Neurophysiol 70: 985–996

Lund JP (1991) Mastication and its control by the brain stem. CritRev Oral Biol Med 2: 33–64

Lund JP, Enomoto S (1988) The generation of mastication by themammalian central nervous system. In: Cohen A, Rossignol S,Grillner S (eds) Neural control of rhythmic movements in ver-tebrates. Wiley, New York, pp 41–72

Lund JP, Donga R, Widmer CG, Stohler CS (1991) The pain-adap-tation model: a discussion of the relationship between chronicmusculoskeletal pain and motor activity. Can J Physiol Phar-macol 69: 683–694

Lund JP, Stohler CS, Widmer CG (1993) The relationship betweenpain and muscle activity in fibromyalgia and similar condi-tions. In: Værøy H, Merskey H (eds) Progress in fibromyalgiaand myofascial pain. Elsevier, Amsterdam, pp 311–327

Luschei ES, Goldberg LJ (1981) Neural mechanisms of mandibu-lar control: mastication and voluntary biting. In: Brooks VB(ed) Handbook of physiology. Motor control, vol 2. AmericanPhysiological Society, Bethesda MD, pp 1237–1274

Møller E, Sheikholeslam A, Lous I (1984) Response of elevatoractivity during mastication to treatment of functional disor-ders. Scand J Dent Res 92: 64–83

Murray GM, Lin L-D, Moustafa EM, Sessle BJ (1991) The effectsof reversible inactivation by cooling of the primate face motorcortex on the performance of a trained tongue-protrusion taskand a trained biting task. J Neurophysiol 65: 511–530

Olsson KÅ, Sasamoto K, Lund JP (1986) Modulation of transmis-sion in rostral trigeminal sensory nuclei during chewing. JNeurophysiol 55: 56–75

Ottenhoff FAM, van der Bilt A, van der Glas HW, Bosman F (1993)Control of human jaw elevator muscle activity during simulatedchewing with varying bolus size. Exp Brain Res 96: 501–512

Reid KI, Gracely RH, Dubner RA (1994) The influence of time, facialside, and location on pain-pressure thresholds in chronic myoge-nous temporomandibular disorder. J Orofacial Pain 8: 258–265

Schwartz G, Lund JP (1995) Modification of rhythmical jawmovements by noxious pressure applied to the periosteum ofthe zygoma in decerebrate rabbits. Pain 63: 153–161

Sessle BJ, Martin RE, Murray GM, Masuda Y, Kemppainen P, Na-rita N, Seo K, Raouf R (1995) Cortical mechanisms control-ling mastication and swallowing in the awake monkey. In:Morimoto T, Matsuya T, Takada K (eds) Brain and oral func-tion. Elsevier, Amsterdam, pp 181–189

Stohler CS, Ashton-Miller JA, Carlson DS (1988) The effects ofpain from the mandibular joint and muscles on masticatorymotor behaviour in man. Arch Oral Biol 33: 175–182

Stohler CS, Wang JS, Veerasarn P (1990) Motor unit behavior inresponses to experimental pain. J Dent Res 69: 273

Svensson P, Arendt-Nielsen L, Houe L (1996) Sensory-motor in-teractions of human experimental unilateral jaw muscle pain: aquantitative analysis. Pain 64: 241–249

Westberg K-G, Olsson KA, Lund JP, Clavelou P (1995) Premoto-neurones in the oral nucleus of the spinal trigeminal tract:functional properties. In: Morimoto T, Matsuya T, Takada K(eds) Brain and oral function. Elsevier, Amsterdam, pp 87–97

Yu X-M, Sessle BJ, Vernon H, Hu JW (1995) Effects of inflamma-tory irritant application to the rat temporomandibular joint onjaw and neck muscle activity. Pain 60: 143–149

Yu X-M, Sessle BJ, Haas DA, Izzo A, Vernon H, Hu JW (1996)Involvement of NMDA receptor mechanisms in jaw electro-myographic activity and plasma extravasation induced by in-flammatory irritant application to temporomandibular joint re-gions of rats. Pain 68: 169–178