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Christian S Stohler

Publications and source records attributed to Christian S Stohler.

16 recordsLinked to original sources
PubMed2006

Variations in the human pain stress experience mediated by ventral and dorsal basal ganglia dopamine activity.

In addition to its involvement in motor control and in encoding reward value, increasing evidence also implicates basal ganglia dopaminergic mechanisms in responses to stress and aversive stimuli. Basal ganglia dopamine (DA) neurotransmission may then respond to environmental events depending on their saliency, orienting the subsequent responses of the organism to both positive and negative stimuli. Here we examined the involvement of DA neurotransmission in the human response to pain, a robust physical and emotional stressor across species. Positron emission tomography with the DA D2 receptor antagonist radiotracer [11C]raclopride detected significant activation of DA release in dorsal and ventral regions of the basal ganglia of healthy volunteers. Activation of nigrostriatal (dorsal nucleus caudate and putamen) DA D2 receptor-mediated neurotransmission was positively associated with individual variations in subjective ratings of sensory and affective qualities of the pain. In contrast, mesolimbic (nucleus accumbens) DA activation, which may impact on both D2 and D3 receptors, was exclusively associated with variations in the emotional responses of the individual during the pain challenge (increases in negative affect and fear ratings). These data demonstrate that basal ganglia dopamine D2 receptor-mediated neurotransmission is involved in responses to pain and that it contributes to individual variations in the pain experience at the levels of physical and emotional elements, albeit with different neuroanatomical substrates.

Adult↗
PubMed2006

Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women.

Prominent interindividual and sex-dependent differences have been described in responses to sustained pain and other stressful stimuli. Variations in mu-opioid receptor-mediated endogenous opioid neurotransmission may underlie some of these processes. We examined both baseline mu-opioid receptor levels and the activation of this neurotransmitter system during sustained pain using positron emission tomography in a sample of young healthy men and women. Women were studied twice, during low and high estrogen states. The high-estrogen state was associated with regional increases in baseline mu-opioid receptor availability in vivo and a greater activation of endogenous opioid neurotransmission during the pain stressor. The latter did not differ from that obtained in males. During the low estrogen condition, however, significant reductions in endogenous opioid tone were observed at the level of thalamus, nucleus accumbens, and amygdala, which were associated with hyperalgesic responses. Estrogen-associated variations in the activity of mu-opioid neurotransmission correlated with individual ratings of the sensory and affective perceptions of the pain and the subsequent recall of that experience. These data demonstrate a significant role of estrogen in modulating endogenous opioid neurotransmission and associated psychophysical responses to a pain stressor in humans.

Adult↗
PubMed2005

Interface of physical and emotional stress regulation through the endogenous opioid system and mu-opioid receptors.

Unraveling the pathways and neurobiological mechanisms that underlie the regulation of physical and emotional stress responses in humans is of critical importance to understand vulnerability and resiliency factors to the development of a number of complex physical and psychopathological states. Dysregulation of central stress response circuits have been implicated in the establishment of conditions as diverse as persistent pain, mood and personality disorders and substance abuse and dependence. The present review examines the contribution of the endogenous opioid system and mu-opioid receptors to the modulation and adaptation of the organism to challenges, such as sustained pain and negative emotional states, which threaten its internal homeostasis. Data accumulated in animal models, and more recently in humans, point to this neurotransmitter system as a critical modulator of the transition from acute (warning signals) to sustained (stressor) environmental adversity. The existence of pathways and regulatory mechanisms common to the regulation of both physical and emotional states transcend classical categorical disease classifications, and point to the need to utilize dimensional, "symptom"-related approximations to their study. Possible future areas of study at the interface of "mind" (cognitive-emotional) and "body" (physical) functions are delineated in this context.

Animals↗
PubMed2005

Belief or Need? Accounting for individual variations in the neurochemistry of the placebo effect.

The activation of pain-suppressive, endogenous opioid neurotransmission after administration of a placebo with expectation of analgesia has been directly demonstrated in humans using molecular imaging techniques in recent work. Regional effects were described in the dorsolateral prefrontal cortex, pregenual anterior cingulate, anterior insula, and nucleus accumbens. However, it was also observed that the magnitude of these responses was subject to substantial individual and regional variation. The present study was undertaken to examine the contribution of various factors to the observed variability in the neurochemical responses to placebo administration. Multiple regression analyses were conducted on data from 19 healthy males to study to what degree expectations of analgesia and various elements of the experience of pain itself, in the absence of placebo, were associated with the individual and brain regional variability in endogenous opioid neurochemical responses to placebo. A model that included affective qualities of pain, the volume of algesic stimulus required to maintain pain over the experimental period within a moderate range, and the internal affective state of the volunteers contributed to 40-68% of the variance in the regional neurochemical responses to placebo. These initial data suggests that in the case of endogenous opioid mediated placebo analgesic responses, the individual experience of pain, in particular its affective elements, the internal affective state of the individuals during pain and a measure of sustained pain sensitivity are important factors contributing to the formation of a placebo effect. Further examination of individual variations in placebo responding will need to take into account the underlying process for which relief is required.

Adult↗
PubMed2005

Placebo effects mediated by endogenous opioid activity on mu-opioid receptors.

Reductions in pain ratings when administered a placebo with expected analgesic properties have been described and hypothesized to be mediated by the pain-suppressive endogenous opioid system. Using molecular imaging techniques, we directly examined the activity of the endogenous opioid system on mu-opioid receptors in humans in sustained pain with and without the administration of a placebo. Significant placebo-induced activation of mu-opioid receptor-mediated neurotransmission was observed in both higher-order and sub-cortical brain regions, which included the pregenual and subgenual rostral anterior cingulate, the dorsolateral prefrontal cortex, the insular cortex, and the nucleus accumbens. Regional activations were paralleled by lower ratings of pain intensity, reductions in its sensory and affective qualities, and in the negative emotional state of the volunteers. These data demonstrate that cognitive factors (e.g., expectation of pain relief) are capable of modulating physical and emotional states through the site-specific activation of mu-opioid receptor signaling in the human brain.

Adult↗
PubMed2005

Prosthodontic research: breaking traditional barriers.

There is considerable concern among leaders in both academia and the prosthodontic profession about the vitality of prosthodontic research and the discipline in general. Many feel that prosthodontics should be focused more on issues of societal significance. In addition, patient-oriented research is becoming more difficult to support within the current climate of ever-lower priority for discipline-based research.A break with traditional lines of enquiry is required, which will entail a corresponding break with established departmental boundaries, to gain access to a multiplicity of complementary skills. Several themes will be crucial in future prosthodontic research: clinical decision making, including health economics; materials science and host response at the implant interface; biocompatibility, functional properties and serviceability of prosthodontic materials; and function and dysfunction of the masticatory system. These themes are at the core of future projects that will address quality-of-life issues related to tooth loss. Prosthodontic researchers will have to be far more aggressive in developing synergistic collaborative arrangements, to align prosthodontic research with the major issues of the day, such as aging of the population, health disparities and access to preventive strategies. Through these collaborations, prosthodontics will remain a flagship discipline within dentistry, and its practitioners will be engaged in the major issues of health care.

Dental Research↗
PubMed2004

Taking stock: from chasing occlusal contacts to vulnerability alleles.

Over the past 70 years, temporomandibular disorders (TMDs) have been subject to shifts in conceptual understanding. Unable to account for disease patterns, the mismatch between case assignment and treatment need, and very different interventions producing similar treatment outcomes (except for the risk to patients), emerging theories make persuasive arguments in support of alternative explanations.

Alleles↗
PubMed2003

COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor.

Responses to pain and other stressors are regulated by interactions between multiple brain areas and neurochemical systems. We examined the influence of a common functional genetic polymorphism affecting the metabolism of catecholamines on the modulation of responses to sustained pain in humans. Individuals homozygous for the met158 allele of the catechol-O-methyltransferase (COMT) polymorphism (val158met) showed diminished regional mu-opioid system responses to pain compared with heterozygotes. These effects were accompanied by higher sensory and affective ratings of pain and a more negative internal affective state. Opposite effects were observed in val158 homozygotes. The COMT val158met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli.

Adult↗
PubMed2002

mu-opioid receptor-mediated antinociceptive responses differ in men and women.

Sex differences in the experience of clinical and experimental pain have been reported. However, the neurobiological sources underlying the variability in pain responses between sexes have not been adequately explored, especially in humans. The endogenous opioid neurotransmitters and mu-opioid receptors are centrally implicated in responses to stress, in the suppression of pain, and in the action of opiate analgesic drugs. Here we examined sex differences in the activation of the mu-opioid system in response to an intensity-controlled sustained deep-tissue pain challenge with positron emission tomography and a mu-opioid receptor-selective radiotracer. Twenty-eight young healthy volunteers (14 men and 14 women) were studied during saline control and pain conditions using a double-blind, randomized, and counterbalanced design. Women were scanned during the early follicular phase of their menstrual cycles after ovulatory cycles. Significant sex differences in the regional activation of the mu-opioid system in response to sustained pain were detected compared with saline controls. Men demonstrated larger magnitudes of mu-opioid system activation than women in the anterior thalamus, ventral basal ganglia, and amygdala. Conversely, women demonstrated reductions in the basal state of activation of the mu-opioid system during pain in the nucleus accumbens, an area previously associated with hyperalgesic responses to the blockade of opioid receptors in experimental animals. These data demonstrate that at matched levels of pain intensity, men and women during their follicular phase differ in the magnitude and direction of response of the mu-opioid system in distinct brain nuclei.

Adult↗
PubMed2001

Muscle pain inhibits cutaneous touch perception.

The processing of noxious and non-noxious sensations differs between chronic pain syndromes, and we believe that studies of sensory processing in the presence of pain will help to clarify the aetiology of the conditions. Here we measured in humans the threshold-level mechanosensitivity in tonic experimental muscle pain. We found (1) that muscle pain induced by hypertonic saline reduced cutaneous threshold-level mechanosensitivity at the site of pain and at the mirror site in the contralateral face, (2) that this effect outlasted the sensation of pain, (3) that it was more pronounced when the painful area was reported to be large, and (4) that the loss of mechanosensitivity was greater in males than females. Comparing our findings to results obtained with other pain models, all classes of nociceptors do not seem to have the same effect on cutaneous mechanosensitivity. The observed threshold-level hypoesthesia is consistent with the hypothesis that the increased mechanical thresholds found in clinic cases of temporomandibular disorders and cervicobrachialgia are a direct result of the activation of muscle nociceptors.

Adult↗
PubMed1992

The effect of experimental muscle pain on the background electrical brain activity.

The purpose of this project was to investigate whether specific effects in the background activity of the brain associated with the experience of pain can be depicted by means of quantitative electroencephalography (EEG). Lasting pain was induced by intramuscular infusion of hypertonic saline. The infusion was titrated to maintain pain for a sufficient time to obtain enough data for meaningful analysis. In a first study on 12 subjects, using a single, blind, repeated measures design with randomization of the administration of isotonic (0.9%) and hypertonic (5%) saline, and with subjects unaware of the fact that one substance was isotonic saline, a statistically significant pain response could be attributed to the administration of hypertonic saline. In a second study on 19 subjects, again using a randomized repeated measures design, topographic EEG measures were examined with respect to experimentally induced pain and pain from memory. Prior to each of these experimental stages, baseline recordings were obtained to satisfy the requirement of the crossover design. In addition to the common frequency bands used in EEG, we also obtained data in the frequency range of 35-100 Hz. The short-term variability of the selected EEG measures and their suitability as a sample estimate were assessed by computing the coefficient of variation from all selected epochs of a given subject at baseline. When compared to baseline, spectral analyzed EEG measures during experimental pain demonstrated statistically significant increases in the beta and 35-100 Hz frequency ranges, most notably at the temporal recording sites. There was no statistically significant difference between the EEG measures for (1) experimental pain vs. pain from memory, and (2) the 2 baseline recordings. The great variability in the topographical aspect of the between-subject response was interpreted as being strongly suggestive of the contamination of EEG measures by phenomena attributed to the jaw, facial and scalp musculature. In fact, Pearson correlation coefficients, as high as 0.92, were found between measures in the frequency band of 35-100 Hz and the beta frequency range. The unexplained variance in the heightened beta cortical power density can be attributed to the vigilance scanning of pain processes. Due to the fact that the statistically significant effect of pain on the topographic EEG measures were not different from imagined pain, we concluded that these effects are non-specific for pain.

Adult↗