Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 3 uppsatser.

The underlying nociceptive mechanisms in temporomandibular joint (TMJ) and masticatory muscles in many pain conditions are still unclear, largely due to the limited study of peripheral and central neural mechanisms affecting craniofacial musculoskeletal tissues. This study provided evidence in support of Hypothesis 1: Peripheral glutamatergic and capsaicin-sensitive mechanisms modulate the properties of primary afferents and brainstem neurons processing deep craniofacial nociceptive information. Effects of glutamate and capsaicin injected into the receptive field of deep craniofacial nociceptive afferents or TMJ of TMJ-responsive nociceptive neurons in trigeminal subnucleus caudalis/upper cervical cord (Vc/UCC) were studied in halothane-anesthetized rats. When injected alone, glutamate and capsaicin activated and induced peripheral sensitization in many afferents. Following glutamate injection, capsaicin-evoked activity was greater than that evoked by capsaicin alone, whereas following capsaicin injection, glutamate-evoked responses were similar to those of glutamate alone. When injected alone, glutamate and capsaicin also activated and induced central sensitization in most Vc/UCC neurons. Following glutamate injection, capsaicin evoked greater activity and less sensitization compared with capsaicin alone, whereas following capsaicin, glutamate was less effective in activating and sensitizing most Vc/UCC neurons. This apparent desensitizing effect of capsaicin on glutamate-evoked excitability of Vc/UCC neurons contrasts with the lack of capsaicin-induced modulation of glutamate-evoked afferent excitability, suggesting that peripheral and central sensitization may be differentially involved in the nociceptive effects of glutamate and capsaicin applied to deep craniofacial tissues. Further evidence of glutamate-capsaicin interactions was documented in the attenuation by TMJ pre-injection of glutamate receptor antagonists of jaw muscle activity reflexly evoked by TMJ injection of capsaicin. Moreover, additional findings support Hypothesis 2: Surgical cutaneous incision modulates the properties of brainstem neurons processing deep craniofacial nociceptive information. TMJ-responsive nociceptive Vc/UCC neurons could be activated by surgical incision of the skin overlying the TMJ and this incision-induced afferent barrage caused nociceptive neurons to be temporarily refractory to further capsaicin-induced central sensitization. These novel findings suggest that peripheral glutamate and capsaicin receptor mechanisms as well as surgical cutaneous incision may be involved in the nociceptive processing of deep craniofacial afferent inputs and may interact to modulate both activation as well as sensitization evoked from these tissues.

The underlying nociceptive mechanisms in temporomandibular joint (TMJ) and masticatory muscles in many pain conditions are still unclear, largely due to the limited study of peripheral and central neural mechanisms affecting craniofacial musculoskeletal tissues. This study provided evidence in support of Hypothesis 1: Peripheral glutamatergic and capsaicin-sensitive mechanisms modulate the properties of primary afferents and brainstem neurons processing deep craniofacial nociceptive information. Effects of glutamate and capsaicin injected into the receptive field of deep craniofacial nociceptive afferents or TMJ of TMJ-responsive nociceptive neurons in trigeminal subnucleus caudalis/upper cervical cord (Vc/UCC) were studied in halothane-anesthetized rats. When injected alone, glutamate and capsaicin activated and induced peripheral sensitization in many afferents. Following glutamate injection, capsaicin-evoked activity was greater than that evoked by capsaicin alone, whereas following capsaicin injection, glutamate-evoked responses were similar to those of glutamate alone. When injected alone, glutamate and capsaicin also activated and induced central sensitization in most Vc/UCC neurons. Following glutamate injection, capsaicin evoked greater activity and less sensitization compared with capsaicin alone, whereas following capsaicin, glutamate was less effective in activating and sensitizing most Vc/UCC neurons. This apparent desensitizing effect of capsaicin on glutamate-evoked excitability of Vc/UCC neurons contrasts with the lack of capsaicin-induced modulation of glutamate-evoked afferent excitability, suggesting that peripheral and central sensitization may be differentially involved in the nociceptive effects of glutamate and capsaicin applied to deep craniofacial tissues. Further evidence of glutamate-capsaicin interactions was documented in the attenuation by TMJ pre-injection of glutamate receptor antagonists of jaw muscle activity reflexly evoked by TMJ injection of capsaicin. Moreover, additional findings support Hypothesis 2: Surgical cutaneous incision modulates the properties of brainstem neurons processing deep craniofacial nociceptive information. TMJ-responsive nociceptive Vc/UCC neurons could be activated by surgical incision of the skin overlying the TMJ and this incision-induced afferent barrage caused nociceptive neurons to be temporarily refractory to further capsaicin-induced central sensitization. These novel findings suggest that peripheral glutamate and capsaicin receptor mechanisms as well as surgical cutaneous incision may be involved in the nociceptive processing of deep craniofacial afferent inputs and may interact to modulate both activation as well as sensitization evoked from these tissues.

Functional magnetic resonance imaging (fMRI) has been widely used to study cortical and subcortical mechanisms related to pain. The pathophysiology of burning mouth disorder (BMD) is not clearly understood. Central neuropathic mechanisms are thought to be main players in BMD. This study aimed to compare the location and extension of brain activation following thermal stimulation of the trigeminal nerve with fMRI blood oxygenation level dependent (BOLD) signal. This study included 8 female patients with BMD and 8 matched pain-free volunteers. Qualitative and quantitative differences in brain activation patterns between the two study groups were demonstrated. There were differences in the activation maps regarding the location of activation, with patients displaying greater BOLD signal changes in the right anterior cingulate cortex (ACC BA 32/24) and bilateral precuneus (pandlt;0.005). The control group showed larger BOLD signal changes in the bilateral thalamus, right middle frontal gyrus, right pre-central gyrus, left lingual gyrus and cerebellum (pandlt;0.005). It was also demonstrated that patients had far less volumetric activation throughout the entire brain compared to the control group. These data are discussed in light of recent findings suggesting brain hypofunction as a key player in chronic neuropathic pain conditions.

Background: Whiplash associated disorders (WAD) account for a large proportion of the overall impairment and disability from traffic injuries and causes substantial bio psychosocial consequences for some individuals. Aims: To increase the knowledge about factors described in terms of either function /impairment, activity/disability and life satisfaction in acute and chronic WAD as well as possible implications for rehabilitation. Within this aim the incidence and recovery rate of whiplash injury and prognostic factors of interest for early rehabilitation have been studied. Subjects and Methods: Fifty-five healthy controls and 34 WAD subjects were analysed within and between groups concerning a) biomechanical out put, endurance, fatigue and muscle tension (EMG activity of trapezius, infraspinatus and deltoideus) during repetitive shoulder forward flexion b) impairments and activity/disability and life satisfaction.356 subjects seeking medical attention due to whiplash trauma, 296 were available at follow up, mean 16 months post injury. Incidence and odds ratio of accident and other background factors on disability were determined. Thirty-four out of 43 patients with whiplash injury were investigated through quantitative sensory tests at six weeks and 71 months after injury. 62 WAD participated in an interdisciplinary rehabilitation program (a pilot study) designed to evaluate such rehabilitation program for patients with chronic (in relatively early stage) WAD. Program evaluation of impairment, disability and life satisfaction (prospective and retrospective) was carried out before and after program and at 6 months. Results: No significant effects of sex or age on the ability to relax between repetitive r muscle contractions (SAR) were found in healthy subjects (study I). Significantly higher inability to relax between contractions was found for the two portions of trapezius and infraspinatus in the WAD group compared to the healthy group (study II). Significantly lower levels of activity preferences were noted for three out of five indices in females with WAD The WAD group had significantly higher prevalence of neropsychological and emotional symptoms. Both pain related symptoms and neropsychological symptoms were of significant importance for aspects of disability and life satisfaction in this group (study IV). Sensory disturbances over the trigeminal skin area persisted over the years. At follow-up a significant correlation was found between the sensory disturbances and the symptoms related to the central nervous system while no significant relationship was found with the musculoskeletal symptoms (study HI) .The annual incidence according to the grading of the Quebec Task Force on Whiplash-Associated Disorders (WAD 1-3) was 3.2/1000 and 4.2/1000 when WAD 0 was included. Sixty-eight percent of the patients recovered during the follow-up Pre-traumatic neck pain, low educational level, female gender and WAD grade E-Ill were significantly associated with a poor prognosis (study IV). . Participants in the rehabilitation program reported increased coping ability. Stress reactions seemed rather frequent (32 %). Pain intensity in the neck and upper back were significantly decreased at 6 months follow-up. However, for most of the functional and psychological markers, no significant changes were found (study V). Conclusion: The higher prevalence of musculoskeletal complaints of the neck shoulder region in females cannot be explained by higher muscle tension and clinical assumption of increased muscle tension seems correct in whiplash patients Results indicate heterogeneity among WAD subjects. Females are at risk after a whiplash trauma but the severity of initial symptoms and signs also affect outcome as well as low education. High levels of neuropsychological symptoms and pain, signs of posttraumatic stress, fear and avoidance, loss of control, anxiety, bio-mechanical and psychosocial factors at work (studies) and social support are potential factors to be aware of. Extensive and costly investigations are in most cases not necessary. However most persons will recover a whiplash injury. Multidisciplinary/interdisciplinary assessment should be considered at three months if substantial negative effect on the person’s ability to function and health situation exists. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 2001, härtill 6 uppsatser.</p> / digitalisering@umu

The role of dopamine in directly modulating somatic motoneuron excitability and hence muscle tone is unknown. We investigated whether dopamine influences the trigeminal motor pool (MoV) that innervates the masseter and tensor palatini muscles, both of which function to maintain upper airway patency. We hypothesized that dopamine facilitates motor outflow at the MoV. We focally applied apomorphine (nonspecific dopamine receptor agonist) at the MoV in anaesthetized rats. We also applied receptor-specific agonists and antagonists to determine the receptor subtype mediating dopaminergic mechanisms of action. We demonstrated that dopaminergic transmission at the MoV potently increased motor outflow via the D1-like receptor and facilitated masseter and tensor palatini muscle tone. It is unknown whether endogenous dopamine release on to airway motoneurons influences their activity to regulate muscle tone in natural sleep-wake behaviours. This issue warrants investigation because the neurochemical basis of upper airway motor dysfunction (e.g. obstructive sleep apnea) remains poorly characterized.

The role of dopamine in directly modulating somatic motoneuron excitability and hence muscle tone is unknown. We investigated whether dopamine influences the trigeminal motor pool (MoV) that innervates the masseter and tensor palatini muscles, both of which function to maintain upper airway patency. We hypothesized that dopamine facilitates motor outflow at the MoV. We focally applied apomorphine (nonspecific dopamine receptor agonist) at the MoV in anaesthetized rats. We also applied receptor-specific agonists and antagonists to determine the receptor subtype mediating dopaminergic mechanisms of action. We demonstrated that dopaminergic transmission at the MoV potently increased motor outflow via the D1-like receptor and facilitated masseter and tensor palatini muscle tone. It is unknown whether endogenous dopamine release on to airway motoneurons influences their activity to regulate muscle tone in natural sleep-wake behaviours. This issue warrants investigation because the neurochemical basis of upper airway motor dysfunction (e.g. obstructive sleep apnea) remains poorly characterized.

Migraine, a neurovascular disorder, is associated with disturbances in brain stem activity during attacks. Interictal persistence of these disturbances might increase vulnerability to recurrent attacks of migraine. To explore this possibility, effects of motion sickness and pain on migrainous symptoms and extracranial vascular reponses were investigated in 27 migraine sufferers in the headache-free interval, and 23 healthy age/sex matched controls. Symptoms of migraine and motion sickness are remarkably similar. As both maladies involve reflexes that relay in the brain stem, they most probably share the same neural circuitry. Furthermore, migraineurs are usually susceptible to motion sickness and, conversely, motion sickness-prone individuals commonly experience migraine. Participants in the present study were exposed to optokinetic stimulation (OKS), a well-established way of inducing symptoms of motion sickness in susceptible individuals. Sensitivity to painful stimulation of the head and hand was also explored. Head pain is a hallmark of a migraine attack and cutaneous allodynia has been observed elsewhere in the body during attacks. The trigeminal nerve is associated with head pain in migraine, and trigeminal activity evokes reflexes that relay in the brain stem. To stimulate the trigeminal nerve, ice was applied to the temple. To stimulate nociceptors elsewhere in the body the participant immersed their fingers and palm in ice-water. Procedures used in this study were physically stressful and probably psychologically stressful. The impact of stress in relation to the development of symptomatic and vascular responses, particularly anticipatory stress-responses, was explored. This research involved one central experiment that consisted of six experimental conditions. On separate occasions participants were exposed to optokinetic stimulation and painful stimulation of the head or limb, individually and in combination. In migraine sufferers, symptomatic responses were enhanced during all procedures involving OKS and during temple pain after OKS, in the presence of residual motion sickness. During trigeminal stimulation independent of OKS, headache initially developed followed by nausea as the procedure progressed. In contrast, symptoms barely developed in controls during any of the six procedures except for slight dizziness, self-motion and visual-illusion during conditions involving OKS, and slight nausea when the temple was painfully stimulated during OKS and during OKS alone. Trigeminal stimulation during OKS intensified nausea and headache in migraine sufferers compared to during OKS alone or limb pain during OKS. However, the remaining symptomatic ratings were not affected by temple pain during OKS, suggesting a specific association between nausea and head pain. It may be that these cardinal symptoms compound one another during a migraine attack. Enhanced symptomatic responses in migraine sufferers during the headache interval may indicate activation of hypersensitive neural pathways that mediate symptoms of motion sickness or migraine. Migraineurs found procedures generally more unpleasant, and ice-induced pain ratings more intense and unpleasant, than controls, which may further indicate hyperexcitable nociception in this group, or a difference in their criterion of discomfort. Vascular responses, particularly during OKS alone, and during painful stimulation independent of OKS, were greater in migraine sufferers than in controls. The added stress of painful stimulation during OKS appeared to boost facial blood flow in controls to approach levels obtained in migraine sufferers. Enhanced vasodilatation was observed in migraineurs prior to painful stimulation, presumably due to anticipatory anxiety. For both groups ipsilateral vascular responses were greater than contralateral responses when the hand was painfully stimulated. During limb pain before OKS asymmetry was minimal in migraine sufferers but more apparent in controls. An enhanced stress response in migraineurs may have drawn ipsilateral and contralateral responses closer together. The development of symptoms during the procedures of this study provides an insight into how symptoms might develop sequentially in a migraine attack. Once the headache is in motion, nausea and headache may mutually exacerbate one another. In turn, trigemino-vascular responses and stress appear to be associated with the migraine crisis. Given the interactive nature of symptomatic, vascular, and stress responses, it may be more effective to target multiple, rather than individual, symptoms, in prophylactic or acute chemical and psychological interventions.

Thesis (M.CM)--Hong Kong Baptist University, 2006. / Dissertation submitted to the School of Chinese Medicine. Includes bibliographical references (leaves 61-63).

Thesis (M.S.)--Missouri State University, 2008. / "May 2008." Includes bibliographical references (leaves 56-63). Also available online.