Norman F. Capra

Experimental muscle pain produces central modulation of proprioceptive signals arising from jaw muscle spindles

&NA; The aim of the present study was to investigate the effects of intramuscular injection with hypertonic saline, a well‐established experimental model for muscle pain, on central processing of proprioceptive input from jaw muscle spindle afferents. Fifty‐seven cells were recorded from the medial edge of the subnucleus interpolaris (Vi) and the adjacent parvicellular reticular formation from 11 adult cats. These cells were characterized as central units receiving jaw muscle spindle input based on their responses to electrical stimulation of the masseter nerve, muscle palpation and jaw stretch. Forty‐five cells, which were successfully tested with 5% hypertonic saline, were categorized as either dynamic‐static (DS) (n=25) or static (S) (n=20) neurons based on their responses to different speeds and amplitudes of jaw movement. Seventy‐six percent of the cells tested with an ipsilateral injection of hypertonic saline showed a significant modulation of mean firing rates (MFRs) during opening and/or holding phases. The most remarkable saline‐induced change was a significant reduction of MFR during the hold phase in S units (100%, 18/18 modulated). Sixty‐nine percent of the DS units (11/16 modulated) also showed significant changes in MFRs limited to the hold phase. However, in the DS neurons, the MFRs increased in seven units and decreased in four units. Finally, five DS neurons showed significant changes of MFRs during both opening and holding phases. Injections of isotonic saline into the ipsilateral masseter muscle had little effect, but hypertonic saline injections made into the contralateral masseter muscle produced similar results to ipsilateral injections with hypertonic saline. These results unequivocally demonstrate that intramuscular injection with an algesic substance, sufficient to produce muscle pain, produces significant changes in the proprioceptive properties of the jaw movement‐related neurons. Potential mechanisms involved in saline‐induced changes in the proprioceptive signals and functional implications of the changes are discussed.

Central connections of trigeminal primary afferent neurons: topographical and functional considerations.

This article reviews literature relating to the central projection of primary afferent neurons of the trigeminal nerve. After a brief description of the major nuclei associated with the trigeminal nerve, the presentation reviews several early issues related to theories of trigeminal organization including modality and somatotopic representation. Recent studies directed toward further definition of central projection patterns of single nerve branches or nerves supplying specific oral and facial tissues are considered together with data from intraaxonal and intracellular studies that define the projection patterns of single fibers. A presentation of recent immunocytochemical data related to primary afferent fibers is described. Finally, several insights that recent studies shed on early theories of trigeminal input are assessed.

Mechanisms of oral sensation

Sensory nerves that supply mechanoreceptors in the mucosal lining of the oral cavity, pharynx, and larynx provide the substrate for a variety of sensations. They are essential for the perception of complex or composite sensory experiences including oral kinesthesia and oral stereognosis. Relevant to the concerns of the oral health care delivery specialist they also contribute to initiation of reflexes and coordination and timing of patterned motor behaviors. The response of oral mechanoreceptors to natural stimuli is determined to a large degree by morphological factors such as the nature of the relationship between nerve ending and certain cellular specializations, their distribution in the mucosa, the diameter of their primary afferent nerve fibers, and the central distribution of these fibers in the brainstem. Because of morphological similarities to certain cutaneous mechanoreceptors, the mucosal lining may be considered as an internal continuation of the large “receptor sheet” for localization and detection of mechanical stimuli. In some regions of the oral, pharyngeal, and laryngeal mucosa, this analogy is appropriate whereas in others, existing data suggest a different role consistent with regionally specific demands (i.e., initiation of protective reflexes).

Human and animal experimental models of acute and chronic muscle pain: intramuscular algesic injection.

Pain of muscle origin is the major presenting symptom of many clinically defined conditions. Intermittent recurring and chronic pain may be regional (e.g. temporomandibular disorders, TMD) or generalized involving most of the body (e.g. fibromyalgia syndrome, FMS). The economic and emotional impact of chronic musculoskeletal pain disorders may be measured in terms of lost productivity and human suffering. Of the experimental strategies used to study muscle pain, intramuscular algesic injection produces quantifiable and clinically relevant pain, hyperalgesia and altered motor function in humans. This method also reliably activates nociceptive pathways and produces nocifensive behaviors in animals. Many algogens used in animal experiments cannot be practically tested in human subjects but these studies have contributed significantly to understanding chronic muscle pain. This review will examine key findings from human and animal intramuscular injection experiments modeling acute and persistent muscle pain, with an emphasis on areas of clinically relevant convergence across models.

Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline

&NA; Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement‐related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probsts tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. Thirty‐five neurons recorded from the Vmes were characterized as muscle spindle afferents based on their responses to passive jaw movements, muscle palpation, and electrical stimulation of the masseter nerve. Each cell was tested by injecting a small volume (250 &mgr;l) of either 5% hypertonic and/or isotonic saline into the receptor‐bearing muscle. Twenty‐nine units were tested with 5% hypertonic saline, of which 79% (23/29) showed significant modulation of mean firing rates (MFRs) during one or more phases of ramp‐and‐hold movements. Among the muscle spindle primary‐like units (n=12), MFRs of 4 units were facilitated, five reduced, two showed mixed responses and one unchanged. In secondary‐like units (n=17), MFRs of 9 were facilitated, three reduced and five unchanged. Thirteen units were tested with isotonic saline, of which 77% showed no significant changes of MFRs. Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.

Development of a behavioral assessment of craniofacial muscle pain in lightly anesthetized rats

&NA; In this study, a new behavioral assessment of craniofacial muscle pain in the lightly anesthetized rat is described. Intramuscular injections with algesic agents in lightly anesthetized rats evoked a characteristic ipsilateral hindpaw shaking behavior for several minutes similar to previously described orofacial pain‐induced grooming behavior in awake rats (Neurosci Lett 103 (1989) 349, Pain 62 (1995) 295). Eighty‐two male Sprague–Dawley rats were used in a series of experiments to study whether this behavior could serve as a valid measure of craniofacial muscle pain. First, we demonstrated that different algesic chemicals, mustard oil (20%), formalin (3%) or hypertonic saline (5%) injected in the mid‐region of the masseter muscle effectively elicited the hindpaw shaking behavior. The behavior was only minimally evoked with vehicle injection. Repeated administrations of hypertonic saline, a short duration non‐sensitizing algogen, demonstrated reproducibility of the assay. Second, we showed that the peak and overall magnitude of the shaking behavior evoked by injections with different concentrations of mustard oil (1 and 5%) changed in a concentration dependent manner. Finally, we showed that systemic administration of morphine sulfate (3 and 0.3 mg/kg, i.p.) dose dependently attenuated mustard oil induced hindpaw‐shaking behavior. Lidocaine injected locally 5 min prior to mustard oil injection also significantly decreased the hindpaw shaking behavior. Based on these results we concluded that ipsilateral hindpaw shaking in lightly anesthetized rats is a stereotypical behavior evoked by noxious muscle stimulation and can be used as a reliable behavioral measure to assess craniofacial muscle pain.

Evidence for subnucleus interpolaris in craniofacial muscle pain mechanisms demonstrated by intramuscular injections with hypertonic saline.

The subnucleus interpolaris (Vi) has been identified as a major recipient for trigeminal ganglionic input from jaw muscles, and contains neurons with nociceptive properties similar to those in the subnucleus caudalis (Vc). Therefore, Vi may be another important site for processing craniofacial muscle nociception. The aims of present study were to define functional properties of Vi neurons that receive input from masseter muscle afferents by characterizing their responses to electrical, mechanical, and to chemical stimulation of the muscle. Ninety cells were identified as masseter muscle units in 11 adult cats. Most of these units (79%) received additional inputs from orofacial skin. Following the intramuscular injection of 5% hypertonic saline, 49% of the cells showed a significant modulation of either the resting discharge and/or responses to innocuous mechanical stimulation on their cutaneous receptive fields (RFs). The most common response to saline injection was an induction or facilitation of resting discharge which declined as an exponential decay function, returning to pre-injection level within 3-4 min. Forty-five percent of the muscle units that were tested with mechanical stimulation (13/29) showed a prolonged inhibition of mechanically-evoked responses. In most cases (8/13), the inhibitory response was accompanied by initial facilitation. The observations that Vi contained a population of neurons that receive small diameter muscle afferent inputs, responded to noxious mechanical stimulation on the muscle and to a chemical irritant that is known to produce pain in humans provide compelling evidence for the involvement of Vi in craniofacial muscle pain mechanisms.

Thermomechanical facilitation of swallowing evoked by electrical nerve stimulation in cats

Application of a cold metal probe to the anterior faucial pillar has been reported to improve swallowing in some patients with dysphagia. Although a variety of stimuli contribute to the initiation of swallowing, the effects of a controlled, cold-thermal stimulus combined with mechanical stimulation have not been examined. It is known that simultaneous stimulation of the glossopharyngeal nerve (IX) and the superior laryngeal nerve may summate to facilitate swallowing in the cat. The goal of this study was to determine whether thermomechanical stimulation of the mucosa innervated by IX would interact with threshold electrical stimulation of the internal laryngeal nerve (ILN) to augment the swallowing response in cats. Four experimental conditions were tested over 24 trials in 4 pentobarbital-anesthetized cats. These included electrical stimulation of ILN, mechanical stimulation of the anterior faucial pillar with a thermode at ambient (room) temperature, concurrent ambient-mechanical and electrical stimulation, and concurrent cold-mechanical and electrical stimulation. Tissue was cooled to 8.9°C during cold-mechanical-electrical stimulation and 25.3°C during ambient-mechanical-electrical and ambient-mechanical alone stimulation. Ambient-mechanical stimulation alone did not produce swallowing. However, both forms of thermomechanical-electrical stimulation elicited a significantly greater number of swallows than did electrical stimulation alone. Therefore, mechanical stimulation with a thermode was capable of modifying the swallowing response in neurologically intact cats. Differences between stimulation with a probe at ambient and at cold temperatures were not significant.

Effects of experimental muscle pain on electromyographic activity of masticatory muscles in the rat

The aim of the present study was to investigate the effects of noxious chemical stimulation of a jaw muscle on postural electromyographic (EMG) activity from several masticatory muscles in lightly anesthetized rats. Unilateral injection of a substance known to induce acute muscle pain (5% NaCl) or longer duration of pain with inflammation (mustard oil) was made into the masseter muscle. The changes in EMG activity following the injection were recorded from the injected and contralateral masseter muscles and the ipsilateral digastric muscle. The algesic chemicals produced a significant but transient increase in EMG activity in all three muscles. The data from the present study and similar observations from clinical and experimental human studies suggest that increased activity from muscle nociceptors is not sufficient to produce a prolonged increase in postural EMG activity. Therefore, the development and maintenance of chronic jaw muscle pain does not appear to result from a feedback cycle mechanism.

The effect of experimental muscle pain on the amplitude and velocity sensitivity of jaw closing muscle spindle afferents

The effect of experimental muscle pain on the amplitude and velocity sensitivity of muscle spindle primary afferent neurons in the trigeminal mesencephalic nucleus (Vmes) was examined. Extracellular recordings were made from 45 neurons designated as spindle primary- or secondary-like on the basis of their response to ramp-and-hold jaw movements. Velocity sensitivity was assessed in spindle primary-like afferents by calculating the mean dynamic index of each unit in response to three different velocities of jaw opening before and after intramuscular injection with hypertonic saline (HS, 5%, 100 microl). The amplitude sensitivity of all jaw muscle spindle afferents was assessed by calculating the mean firing rate of each unit in response to three different amplitudes of jaw openings during both the open and hold phases of the movement and with best-fit lines obtained, using linear regression analysis, before and after HS injection. The variance of the two regression lines obtained for each unit before and after the injection was compared using the coincidence test, and changes in intercept and slope were determined. Seventy-five percent of the primary-like units and 80% of the secondary-like units presented with changes in static behavior after HS injection. Thirty-six percent of the primary-like units showed changes in dynamic behavior. Injection of isotonic saline (control) did not alter the responses of the spindle afferent to jaw opening. Thus, our results demonstrate that the predominant effect of noxious stimulation was a shift in the amplitude sensitivity of both spindle primary-like and secondary-like afferents and, to a lesser extent, the velocity sensitivity of the spindle primary-like unit. In accordance with earlier studies in the cat hindlimb and neck muscles, these results suggest that the activation of masseter muscle nociceptor alters spindle afferent responses to stretch acting primarily through static gamma motor neurons.