Growing evidence suggests that astroglia are involved in pain states, but no studies have tested ... more Growing evidence suggests that astroglia are involved in pain states, but no studies have tested their possible involvement in modulating the activity of nociceptive neurons per se. This study has demonstrated that the central sensitization induced in functionally identified nociceptive neurons in trigeminal subnucleus caudalis (the medullary dorsal horn) by application of an inflammatory irritant to the rat's tooth pulp can be significantly attenuated by continuous intrathecal superfusion of methionine sulfoximine (MSO; 0.1 mM), an inhibitor of the astroglial enzyme glutamine synthetase that is involved in the glutamate-glutamine shuttle. Simultaneous superfusion of MSO and glutamine (0.25 mM) restored the irritant-induced central sensitization. In control experiments, superfusion of either MSO or glutamine alone, or vehicle, did not produce any significant changes in neuronal properties. These findings suggest that the astroglial glutamateglutamine shuttle is essential for the initiation of inflammation-induced central sensitization but that inhibition of astroglial function may not affect normal nociceptive processing.
Journal of manipulative and physiological therapeutics
To determine if the activity of jaw and neck muscles in a rat model is influenced by the applicat... more To determine if the activity of jaw and neck muscles in a rat model is influenced by the application of small-fiber irritant mustard oil to meningeal/dural vascular tissues. Controlled animal experiment. University neurophysiology laboratory. Applications of mineral oil (vehicle control) and mustard oil to exposed meningeal/dural vascular tissues. Electromygraphic (EMG) recordings from deep suboccipital muscles, bilaterally, and the left trapezius and left masseter muscles. Mineral oil evoked no EMG responses in any muscles. The incidences of mustard oil-evoked EMG increases were 100%, 100%, 89% and 78% for left deep neck, right deep neck, left trapezium and left masseter muscles, respectively. The durations of EMG responses were (mean +/- SD) 19.2 +/- 6.6 min, 17.3 +/- 7.5 min, 14.5 +/- 6.8 min and 12.7 +/- 8.5 min, respectively. These results document that meningeal/dural vascular irritation leads to sustained and reversible activation of neck and jaw muscles that may be related t...
A study was carried out in 19 anaesthetized rats to determine if the electromyographic (EMG) acti... more A study was carried out in 19 anaesthetized rats to determine if the electromyographic (EMG) activity of jaw and neck muscles could be influenced by injection of the inflammatory irritant mustard oil into deep paraspinal tissues surrounding the Cl-3 vertebrae. The EMG activity was recorded ipsilaterally in the digastric, masseter and trapezius muscles and bilaterally in deep neck muscles (rectus capitis posterior). In comparison with control (vehicle) injections, mustard oil (20 ~1, 20%) injected into the deep paraspinal tissues induced significant increases in EMG activity in the neck muscles in all the animals and in the jaw muscles in the majority of the animals; the effects of mustard oil were more prominent in the former. The EMG response evoked by mustard oil injection was frequently reflected in two phases of enhanced activity. The early phase of the increase in EMG activity was usually initiated immediately following mustard oil injection (mean latency: 20.4 + 17.7 set) and lasted 1.6 k 1.1 min. The second phase occurred 11.3 f 7.6 min later and lasted 11.0 f 8.1 min. Evans Blue extravasation was apparent in the deep paraspinal tissues surrounding the Cl-3 vertebrae after mustard oil injection, and histological examination showed that mustard oil injection induced an inflammatory reaction in the rectus capitis posterior muscle. These results document that injection of the inflammatory irritant mustard oil into deep paraspinal tissues results in a sustained and reversible activation of both jaw and neck muscles. Such effects may be related to the reported clinical occurrence of increased muscle activity associated with trauma to deep tissues.
We have recently demonstrated that deafferentation of the adult cat's maxillary or mandibular pos... more We have recently demonstrated that deafferentation of the adult cat's maxillary or mandibular posterior tooth pulps results in statistically significant changes in mechanoreceptive field and response properties of low-threshold mechanoreceptive (LTM) brainstem neurons in trigeminal (V) subnucleus oralis. These effects were however reversible, and the statistically significant changes were apparent only for 1-2 weeks after the deafferentation procedure. The aim of this study was to examine the effects of a more extensive deafferentation involving both maxillary and mandibular pulps. In accordance with our earlier study, the pulps of the teeth were deafferented and, in a 'blind' design, the physiological properties of oralis LTM neurons were studied in each of these animals and compared with those from control, unoperated cats. Statistically significant changes in mechanoreceptive field and response properties were produced in these animals with both maxillary and mandibular quadrants deafferented and were similar to those documented in our earlier study involving deafferentation of only one quadrant. However, as well as occurring at 1-2 weeks after the deafferentation procedures, the changes were still apparent at 4 weeks following the deafferentation. In addition, we also documented that changes could be produced by a two-stage deafferentation procedure involving first the mandibular pulps and then, 3 weeks later, the maxillary pulPs. These findings thus demonstrate that an extensive deafferentation procedure involving mandibular as well as maxillary tooth pulps can produce statistically significant changes in the physiological properties of V brainstem neurons of adult cats that may last at least 4 weeks postoperatively.
An electromyographic (EMG) study was carried out in 40 anaesthetized rats to determine if the act... more An electromyographic (EMG) study was carried out in 40 anaesthetized rats to determine if the activity of jaw and neck muscles could be influenced by injection of the small-fibre excitant and inflammatory irritant mustard oil into the region of the temporomandibular joint (TMJ). Injection of a vehicle (mineral oil, 20 tzl) did not produce any significant change in EMG activity. In contrast, injection of mustard oil (20/zl, 20%) evoked increases in EMG activity in the jaw muscles but not in the neck muscles. The increased EMG activity evoked by mustard oil was reflected in 1 or 2 phases of increased activity. The early EMG increase occurred soon after the mustard oil injection (mean latency + SD: 3.5 + 2.3 sec), peaked within 1 min, and then subsided (mean duration: 7.5 + 5.2 min). The later EMG increase occurred at 14.6 + 10.0 min after the mustard oil injection and lasted 14.3 + 12.3 min. These excitatory effects of mustard oil on the EMG activity of jaw muscles appear to have a reflex basis since they could be abolished by pre-administration of local anaesthetic into the TMJ region. These results document that TMJ injection of mustard oil results in a sustained and reversible activation of jaw muscles that may be related to the reported clinical occurrence of increased muscle activity associated with trauma to the TMJ.
Objective: Since there is limited information of the effects of orofacial pain on oromotor behavi... more Objective: Since there is limited information of the effects of orofacial pain on oromotor behaviour, the aim of this study was to test the effects of injection of the algesic chemical glutamate into orofacial tissues on licking behaviour in rats. Design: Male Sprague-Dawley rats were trained to carry out stereotyped licking from a water spout connected to a force transducer, and once they met preset licking motor requirements (peak force of licking of 2-20 g, interlick interval of 0.11-0.19 s), their masseter muscle or tongue was injected with either isotonic saline (0.9%, 5 mL) or glutamate (1.0 M, 5 mL) and several parameters of their licking performance were reassessed. Results: There were significant effects (P < 0.05; 1-way repeated measures ANOVA) of glutamate injection into the tongue on the number of clusters of licks, the number of licks per cluster, the intercluster period, the peak force of licking and the interlick interval, but there were no significant (P > 0.05) effects on licking of isotonic saline injection into the tongue or isotonic saline or glutamate injection into the masseter muscle. Conclusions: These findings provide the first documentation that noxious stimulation of the tongue, but not of the masseter muscle, has a modulatory effect on licking behaviour in the rat and suggest that the neural substrate for licking may be sensitive to selective nociceptive inputs from the orofacial region.
Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the ef... more Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the effects of surgical cutaneous injury on central nociceptive processing of deep afferent inputs evoked by noxious stimuli such as capsaicin. Thus our aim was to test the effect of surgical cutaneous incision in influencing central sensitization induced by capsaicin injection into the temporomandibular joint (TMJ). The activity of single nociceptive neurons activated by noxious mechanical stimulation of the TMJ was recorded in the trigeminal subnucleus caudalis/upper cervical cord of halothane-anesthetized rats. The cutaneous mechanoreceptive field (RF), cutaneous mechanical activation threshold (MAT) and TMJ MAT of neurons before and after both surgical cutaneous incision alone and capsaicin injection were compared with results of incision and lidocaine pretreatment of the facial skin overlying the TMJ and capsaicin injection into the TMJ. Incision itself induced a barrage of neuronal spikes and excitability increases reflecting central sensitization (cutaneous RF expansion, cutaneous MAT reduction) in most neurons tested whereas lidocaine pretreatment significantly attenuated the barrage and central sensitization. Capsaicin injection into the TMJ induced cutaneous RF expansion, cutaneous MAT reduction and TMJ MAT reduction following lidocaine pretreatment of the cutaneous incision site whereas capsaicin injection following incision alone not only failed to induce further central sensitization but also decreased the existing incision-induced central sensitization (no cutaneous RF expansion, increased cutaneous MAT and TMJ MAT) in most neurons tested. These findings suggest that central sensitization induced by capsaicin alone or by cutaneous incision alone can readily occur in TMJ-responsive nociceptive neurons and that following incision-induced excitability increases, capsaicin may result in a temporary suppression of nociceptive neuronal changes reflecting central sensitization.
Previously, we have demonstrated (Hu et al., 1993) that injection of the small-fiber excitant and... more Previously, we have demonstrated (Hu et al., 1993) that injection of the small-fiber excitant and inflammatory irritant mustard oil (MO) into deep paraspinal tissues surrounding C1-C2 vertebrae can evoke a sustained and reversible increase of electromyographic (EMG) activity of neck and jaw muscles, and can also produce an acute inflammatory response. This increased EMG activity lasts up to 20 min; within 30 min following MO injection, the activity returns to preinjection levels. The aim of our present study was to determine whether an opioid suppressive mechanism may be involved in limiting the increased EMG activity, despite the presence of an ongoing inflammatory response. Three doses (0.6 mg/kg, 1.2 mg/kg, and 2.5 mg/kg) of the opioid antagonist naloxone, along with vehicle (saline), were administered intravenously to determine whether naloxone is capable of inducing a significant recurrence (&quot;rekindling&quot; effect) of EMG activity. A dose-dependent process in the naloxone-induced rekindling effect was demonstrated for the area under the curve of rectified and integrated EMG activity. At the highest dose (2.5 mg/kg), the relative area of naloxone-evoked EMG activity increases reached 83% of the original MO-induced EMG activity level. These results suggest that a central opioid suppressive mechanism is activated by the MO-induced small-afferent barrage, and that this may limit the duration and magnitude of the evoked EMG changes.
The purpose of this study was to evaluate the effect of local anesthetic blockade of afferent inn... more The purpose of this study was to evaluate the effect of local anesthetic blockade of afferent innervation on the development of capsaicin-induced edema in the rat temporomandibular joint (TMJ) region and on reflex jaw muscle activity. Under halothane anesthesia, 64 male Sprague-Dawley rats were prepared for monitoring of edema development by lateral movement of a needle overlying the left TMJ region and for acute recording of electromyographic activity in ipsilateral digastric and masseter muscles. A double-barrel catheter was inserted into the TMJ region for delivery of saline or 0.5% bupivacaine from 1 needle, followed with the injection of 1% capsaicin, 0.1% capsaicin, or vehicle control from the other needle 5 minutes later. Application of capsaicin into the saline pretreated TMJ region led to dose-dependent edema development and reflex jaw muscle activity; however, only 1% capsaicin solution resulted in significant tissue expansion and muscle activity when compared with the vehicle control. Pretreatment of the rat TMJ region with bupivacaine failed to inhibit capsaicin-induced edema development, although successful blockade of nerve conduction was confirmed with the absence of reflex jaw muscle activity. Capsaicin-induced edema of the rat TMJ region developed independent of axonal conduction, suggesting neurogenic inflammation may arise regardless of functional nerve conduction.
Purinergic receptors are involved in tooth-pulp evoked nocifensive behavior and brainstem neurona... more Purinergic receptors are involved in tooth-pulp evoked nocifensive behavior and brainstem neuronal activity
The trigeminal nerve (Vn) is the largest and most complex of the 12 cranial nerves. Although the ... more The trigeminal nerve (Vn) is the largest and most complex of the 12 cranial nerves. Although the V and spinal systems share the general function of relaying somatic sensory information from the head and lower body, respectively, to the central nervous system there exist significant organizational differences of both a qualitative and quantitative nature that argue against the notion of the V system as simply a rostral extension of the spinal cord. The peripheral and central components of the sensory V system are organized to warn the organism against changing environmental conditions. In addition to supplying sensory fibers to all craniofacial tissues, the Vn also innervates all specialized sense organs of the head such as the retina, cochlea, taste papillas, and olfactory epithelium. The diversity arrangement of Vn endings in craniofacial tissues range from penetrating to the outermost layers of the corneal epithelium capable of responding to the slightest changes in temperature, environmental chemicals, or foreign body intrusion to endings in the dental pulp that are housed within a tough enamel coat and become sensitive to external stimuli only after injury. The central organization of Vn afferents is quite unlike that at spinal levels in that a somatotopic map of the head and oral cavity is preserved at multiple rostrocaudal levels of the trigeminal sensory brainstem nuclear complex (TSNC). The most caudal portion of the TSNC, trigeminal subnucleus caudalis (Vc), receives extensive convergent input from cranial nerves V, VII, IX, and X as well as from upper cervical rootlets, and is the preferential terminal zone for the majority of small unmyelinated sensory fibers that convey mainly nociceptive information. The Vn system is tightly coupled to the autonomic nervous system, especially the parasympathetic outflow. Unlike spinal nerves, some Vn afferents project without interruption to autonomic control regions of the lower brainstem such as the nucleus tractus solitarius (NTS), while in the periphery blood flow to the face is under a robust vasodilatory control system. Many chronic pain conditions involving the Vn system such as migraine headache and temporomandibular joint disorders are distinguished by a higher prevalence in women than men and a strong linkage to autonomic and endocrine controls. Trigeminal mechanisms of nociception: peripheral and brainstem organization
1. The aim of this study was to determine whether there are differential neuroplastic effects of ... more 1. The aim of this study was to determine whether there are differential neuroplastic effects of cutaneous and deep stimuli on the mechanoreceptive field (RF) properties of nociceptive brain stem neurons recorded in trigeminal (V) subnucleus caudalis. 2. A total of 31 caudalis neurons were functionally identified in anesthetized rats as nociceptive neurons receiving convergent cutaneous and deep afferent inputs, and the effects of the small-fiber excitant and inflammatory irritant mustard oil applied to either tongue muscle or facial skin were tested on their cutaneous and deep RFs. 3. The expression of neuroplasticity on the cutaneous and deep RFs of the neurons was found to depend on the site of application of this irritant. Mustard oil injected into the tongue muscle produced a significant and reversible expansion of both the cutaneous and deep RFs. In contrast, application of mustard oil to facial skin resulted in a significant and reversible expansion of the cutaneous RF, but n...
The effects of inferior alveolar nerve (IAN) transection on escape behavior and MDH neuronal acti... more The effects of inferior alveolar nerve (IAN) transection on escape behavior and MDH neuronal activity to noxious and nonnoxious stimulation of the face were precisely analyzed. Relative thresholds for escape from mechanical stimulation applied to the whisker pad area ipsilateral to the transection were significantly lower than that for the contralateral and sham-operated whisker pad until 28 days after the transection, then returned to the preoperative level at 40 days after transection. A total of 540 neurons were recorded from the medullary dorsal horn (MDH) of the nontreated naive rats [low-threshold mechanoreceptive (LTM), 27; wide dynamic range (WDR), 31; nociceptive specific (NS), 11] and sham-operated rats with skin incision (LTM, 34; WDR, 30; NS, 23) and from the ipsilateral (LTM, 82; WDR, 82; NS, 31) and contralateral MDH relative to the IAN transection (LTM, 77; WDR, 82; NS, 33). The electrophysiological properties of these neurons were precisely analyzed. Background activ...
Growing evidence suggests that astroglia are involved in pain states, but no studies have tested ... more Growing evidence suggests that astroglia are involved in pain states, but no studies have tested their possible involvement in modulating the activity of nociceptive neurons per se. This study has demonstrated that the central sensitization induced in functionally identified nociceptive neurons in trigeminal subnucleus caudalis (the medullary dorsal horn) by application of an inflammatory irritant to the rat's tooth pulp can be significantly attenuated by continuous intrathecal superfusion of methionine sulfoximine (MSO; 0.1 mM), an inhibitor of the astroglial enzyme glutamine synthetase that is involved in the glutamate-glutamine shuttle. Simultaneous superfusion of MSO and glutamine (0.25 mM) restored the irritant-induced central sensitization. In control experiments, superfusion of either MSO or glutamine alone, or vehicle, did not produce any significant changes in neuronal properties. These findings suggest that the astroglial glutamateglutamine shuttle is essential for the initiation of inflammation-induced central sensitization but that inhibition of astroglial function may not affect normal nociceptive processing.
Journal of manipulative and physiological therapeutics
To determine if the activity of jaw and neck muscles in a rat model is influenced by the applicat... more To determine if the activity of jaw and neck muscles in a rat model is influenced by the application of small-fiber irritant mustard oil to meningeal/dural vascular tissues. Controlled animal experiment. University neurophysiology laboratory. Applications of mineral oil (vehicle control) and mustard oil to exposed meningeal/dural vascular tissues. Electromygraphic (EMG) recordings from deep suboccipital muscles, bilaterally, and the left trapezius and left masseter muscles. Mineral oil evoked no EMG responses in any muscles. The incidences of mustard oil-evoked EMG increases were 100%, 100%, 89% and 78% for left deep neck, right deep neck, left trapezium and left masseter muscles, respectively. The durations of EMG responses were (mean +/- SD) 19.2 +/- 6.6 min, 17.3 +/- 7.5 min, 14.5 +/- 6.8 min and 12.7 +/- 8.5 min, respectively. These results document that meningeal/dural vascular irritation leads to sustained and reversible activation of neck and jaw muscles that may be related t...
A study was carried out in 19 anaesthetized rats to determine if the electromyographic (EMG) acti... more A study was carried out in 19 anaesthetized rats to determine if the electromyographic (EMG) activity of jaw and neck muscles could be influenced by injection of the inflammatory irritant mustard oil into deep paraspinal tissues surrounding the Cl-3 vertebrae. The EMG activity was recorded ipsilaterally in the digastric, masseter and trapezius muscles and bilaterally in deep neck muscles (rectus capitis posterior). In comparison with control (vehicle) injections, mustard oil (20 ~1, 20%) injected into the deep paraspinal tissues induced significant increases in EMG activity in the neck muscles in all the animals and in the jaw muscles in the majority of the animals; the effects of mustard oil were more prominent in the former. The EMG response evoked by mustard oil injection was frequently reflected in two phases of enhanced activity. The early phase of the increase in EMG activity was usually initiated immediately following mustard oil injection (mean latency: 20.4 + 17.7 set) and lasted 1.6 k 1.1 min. The second phase occurred 11.3 f 7.6 min later and lasted 11.0 f 8.1 min. Evans Blue extravasation was apparent in the deep paraspinal tissues surrounding the Cl-3 vertebrae after mustard oil injection, and histological examination showed that mustard oil injection induced an inflammatory reaction in the rectus capitis posterior muscle. These results document that injection of the inflammatory irritant mustard oil into deep paraspinal tissues results in a sustained and reversible activation of both jaw and neck muscles. Such effects may be related to the reported clinical occurrence of increased muscle activity associated with trauma to deep tissues.
We have recently demonstrated that deafferentation of the adult cat's maxillary or mandibular pos... more We have recently demonstrated that deafferentation of the adult cat's maxillary or mandibular posterior tooth pulps results in statistically significant changes in mechanoreceptive field and response properties of low-threshold mechanoreceptive (LTM) brainstem neurons in trigeminal (V) subnucleus oralis. These effects were however reversible, and the statistically significant changes were apparent only for 1-2 weeks after the deafferentation procedure. The aim of this study was to examine the effects of a more extensive deafferentation involving both maxillary and mandibular pulps. In accordance with our earlier study, the pulps of the teeth were deafferented and, in a 'blind' design, the physiological properties of oralis LTM neurons were studied in each of these animals and compared with those from control, unoperated cats. Statistically significant changes in mechanoreceptive field and response properties were produced in these animals with both maxillary and mandibular quadrants deafferented and were similar to those documented in our earlier study involving deafferentation of only one quadrant. However, as well as occurring at 1-2 weeks after the deafferentation procedures, the changes were still apparent at 4 weeks following the deafferentation. In addition, we also documented that changes could be produced by a two-stage deafferentation procedure involving first the mandibular pulps and then, 3 weeks later, the maxillary pulPs. These findings thus demonstrate that an extensive deafferentation procedure involving mandibular as well as maxillary tooth pulps can produce statistically significant changes in the physiological properties of V brainstem neurons of adult cats that may last at least 4 weeks postoperatively.
An electromyographic (EMG) study was carried out in 40 anaesthetized rats to determine if the act... more An electromyographic (EMG) study was carried out in 40 anaesthetized rats to determine if the activity of jaw and neck muscles could be influenced by injection of the small-fibre excitant and inflammatory irritant mustard oil into the region of the temporomandibular joint (TMJ). Injection of a vehicle (mineral oil, 20 tzl) did not produce any significant change in EMG activity. In contrast, injection of mustard oil (20/zl, 20%) evoked increases in EMG activity in the jaw muscles but not in the neck muscles. The increased EMG activity evoked by mustard oil was reflected in 1 or 2 phases of increased activity. The early EMG increase occurred soon after the mustard oil injection (mean latency + SD: 3.5 + 2.3 sec), peaked within 1 min, and then subsided (mean duration: 7.5 + 5.2 min). The later EMG increase occurred at 14.6 + 10.0 min after the mustard oil injection and lasted 14.3 + 12.3 min. These excitatory effects of mustard oil on the EMG activity of jaw muscles appear to have a reflex basis since they could be abolished by pre-administration of local anaesthetic into the TMJ region. These results document that TMJ injection of mustard oil results in a sustained and reversible activation of jaw muscles that may be related to the reported clinical occurrence of increased muscle activity associated with trauma to the TMJ.
Objective: Since there is limited information of the effects of orofacial pain on oromotor behavi... more Objective: Since there is limited information of the effects of orofacial pain on oromotor behaviour, the aim of this study was to test the effects of injection of the algesic chemical glutamate into orofacial tissues on licking behaviour in rats. Design: Male Sprague-Dawley rats were trained to carry out stereotyped licking from a water spout connected to a force transducer, and once they met preset licking motor requirements (peak force of licking of 2-20 g, interlick interval of 0.11-0.19 s), their masseter muscle or tongue was injected with either isotonic saline (0.9%, 5 mL) or glutamate (1.0 M, 5 mL) and several parameters of their licking performance were reassessed. Results: There were significant effects (P < 0.05; 1-way repeated measures ANOVA) of glutamate injection into the tongue on the number of clusters of licks, the number of licks per cluster, the intercluster period, the peak force of licking and the interlick interval, but there were no significant (P > 0.05) effects on licking of isotonic saline injection into the tongue or isotonic saline or glutamate injection into the masseter muscle. Conclusions: These findings provide the first documentation that noxious stimulation of the tongue, but not of the masseter muscle, has a modulatory effect on licking behaviour in the rat and suggest that the neural substrate for licking may be sensitive to selective nociceptive inputs from the orofacial region.
Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the ef... more Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the effects of surgical cutaneous injury on central nociceptive processing of deep afferent inputs evoked by noxious stimuli such as capsaicin. Thus our aim was to test the effect of surgical cutaneous incision in influencing central sensitization induced by capsaicin injection into the temporomandibular joint (TMJ). The activity of single nociceptive neurons activated by noxious mechanical stimulation of the TMJ was recorded in the trigeminal subnucleus caudalis/upper cervical cord of halothane-anesthetized rats. The cutaneous mechanoreceptive field (RF), cutaneous mechanical activation threshold (MAT) and TMJ MAT of neurons before and after both surgical cutaneous incision alone and capsaicin injection were compared with results of incision and lidocaine pretreatment of the facial skin overlying the TMJ and capsaicin injection into the TMJ. Incision itself induced a barrage of neuronal spikes and excitability increases reflecting central sensitization (cutaneous RF expansion, cutaneous MAT reduction) in most neurons tested whereas lidocaine pretreatment significantly attenuated the barrage and central sensitization. Capsaicin injection into the TMJ induced cutaneous RF expansion, cutaneous MAT reduction and TMJ MAT reduction following lidocaine pretreatment of the cutaneous incision site whereas capsaicin injection following incision alone not only failed to induce further central sensitization but also decreased the existing incision-induced central sensitization (no cutaneous RF expansion, increased cutaneous MAT and TMJ MAT) in most neurons tested. These findings suggest that central sensitization induced by capsaicin alone or by cutaneous incision alone can readily occur in TMJ-responsive nociceptive neurons and that following incision-induced excitability increases, capsaicin may result in a temporary suppression of nociceptive neuronal changes reflecting central sensitization.
Previously, we have demonstrated (Hu et al., 1993) that injection of the small-fiber excitant and... more Previously, we have demonstrated (Hu et al., 1993) that injection of the small-fiber excitant and inflammatory irritant mustard oil (MO) into deep paraspinal tissues surrounding C1-C2 vertebrae can evoke a sustained and reversible increase of electromyographic (EMG) activity of neck and jaw muscles, and can also produce an acute inflammatory response. This increased EMG activity lasts up to 20 min; within 30 min following MO injection, the activity returns to preinjection levels. The aim of our present study was to determine whether an opioid suppressive mechanism may be involved in limiting the increased EMG activity, despite the presence of an ongoing inflammatory response. Three doses (0.6 mg/kg, 1.2 mg/kg, and 2.5 mg/kg) of the opioid antagonist naloxone, along with vehicle (saline), were administered intravenously to determine whether naloxone is capable of inducing a significant recurrence (&quot;rekindling&quot; effect) of EMG activity. A dose-dependent process in the naloxone-induced rekindling effect was demonstrated for the area under the curve of rectified and integrated EMG activity. At the highest dose (2.5 mg/kg), the relative area of naloxone-evoked EMG activity increases reached 83% of the original MO-induced EMG activity level. These results suggest that a central opioid suppressive mechanism is activated by the MO-induced small-afferent barrage, and that this may limit the duration and magnitude of the evoked EMG changes.
The purpose of this study was to evaluate the effect of local anesthetic blockade of afferent inn... more The purpose of this study was to evaluate the effect of local anesthetic blockade of afferent innervation on the development of capsaicin-induced edema in the rat temporomandibular joint (TMJ) region and on reflex jaw muscle activity. Under halothane anesthesia, 64 male Sprague-Dawley rats were prepared for monitoring of edema development by lateral movement of a needle overlying the left TMJ region and for acute recording of electromyographic activity in ipsilateral digastric and masseter muscles. A double-barrel catheter was inserted into the TMJ region for delivery of saline or 0.5% bupivacaine from 1 needle, followed with the injection of 1% capsaicin, 0.1% capsaicin, or vehicle control from the other needle 5 minutes later. Application of capsaicin into the saline pretreated TMJ region led to dose-dependent edema development and reflex jaw muscle activity; however, only 1% capsaicin solution resulted in significant tissue expansion and muscle activity when compared with the vehicle control. Pretreatment of the rat TMJ region with bupivacaine failed to inhibit capsaicin-induced edema development, although successful blockade of nerve conduction was confirmed with the absence of reflex jaw muscle activity. Capsaicin-induced edema of the rat TMJ region developed independent of axonal conduction, suggesting neurogenic inflammation may arise regardless of functional nerve conduction.
Purinergic receptors are involved in tooth-pulp evoked nocifensive behavior and brainstem neurona... more Purinergic receptors are involved in tooth-pulp evoked nocifensive behavior and brainstem neuronal activity
The trigeminal nerve (Vn) is the largest and most complex of the 12 cranial nerves. Although the ... more The trigeminal nerve (Vn) is the largest and most complex of the 12 cranial nerves. Although the V and spinal systems share the general function of relaying somatic sensory information from the head and lower body, respectively, to the central nervous system there exist significant organizational differences of both a qualitative and quantitative nature that argue against the notion of the V system as simply a rostral extension of the spinal cord. The peripheral and central components of the sensory V system are organized to warn the organism against changing environmental conditions. In addition to supplying sensory fibers to all craniofacial tissues, the Vn also innervates all specialized sense organs of the head such as the retina, cochlea, taste papillas, and olfactory epithelium. The diversity arrangement of Vn endings in craniofacial tissues range from penetrating to the outermost layers of the corneal epithelium capable of responding to the slightest changes in temperature, environmental chemicals, or foreign body intrusion to endings in the dental pulp that are housed within a tough enamel coat and become sensitive to external stimuli only after injury. The central organization of Vn afferents is quite unlike that at spinal levels in that a somatotopic map of the head and oral cavity is preserved at multiple rostrocaudal levels of the trigeminal sensory brainstem nuclear complex (TSNC). The most caudal portion of the TSNC, trigeminal subnucleus caudalis (Vc), receives extensive convergent input from cranial nerves V, VII, IX, and X as well as from upper cervical rootlets, and is the preferential terminal zone for the majority of small unmyelinated sensory fibers that convey mainly nociceptive information. The Vn system is tightly coupled to the autonomic nervous system, especially the parasympathetic outflow. Unlike spinal nerves, some Vn afferents project without interruption to autonomic control regions of the lower brainstem such as the nucleus tractus solitarius (NTS), while in the periphery blood flow to the face is under a robust vasodilatory control system. Many chronic pain conditions involving the Vn system such as migraine headache and temporomandibular joint disorders are distinguished by a higher prevalence in women than men and a strong linkage to autonomic and endocrine controls. Trigeminal mechanisms of nociception: peripheral and brainstem organization
1. The aim of this study was to determine whether there are differential neuroplastic effects of ... more 1. The aim of this study was to determine whether there are differential neuroplastic effects of cutaneous and deep stimuli on the mechanoreceptive field (RF) properties of nociceptive brain stem neurons recorded in trigeminal (V) subnucleus caudalis. 2. A total of 31 caudalis neurons were functionally identified in anesthetized rats as nociceptive neurons receiving convergent cutaneous and deep afferent inputs, and the effects of the small-fiber excitant and inflammatory irritant mustard oil applied to either tongue muscle or facial skin were tested on their cutaneous and deep RFs. 3. The expression of neuroplasticity on the cutaneous and deep RFs of the neurons was found to depend on the site of application of this irritant. Mustard oil injected into the tongue muscle produced a significant and reversible expansion of both the cutaneous and deep RFs. In contrast, application of mustard oil to facial skin resulted in a significant and reversible expansion of the cutaneous RF, but n...
The effects of inferior alveolar nerve (IAN) transection on escape behavior and MDH neuronal acti... more The effects of inferior alveolar nerve (IAN) transection on escape behavior and MDH neuronal activity to noxious and nonnoxious stimulation of the face were precisely analyzed. Relative thresholds for escape from mechanical stimulation applied to the whisker pad area ipsilateral to the transection were significantly lower than that for the contralateral and sham-operated whisker pad until 28 days after the transection, then returned to the preoperative level at 40 days after transection. A total of 540 neurons were recorded from the medullary dorsal horn (MDH) of the nontreated naive rats [low-threshold mechanoreceptive (LTM), 27; wide dynamic range (WDR), 31; nociceptive specific (NS), 11] and sham-operated rats with skin incision (LTM, 34; WDR, 30; NS, 23) and from the ipsilateral (LTM, 82; WDR, 82; NS, 31) and contralateral MDH relative to the IAN transection (LTM, 77; WDR, 82; NS, 33). The electrophysiological properties of these neurons were precisely analyzed. Background activ...
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