It has been argued that emotion, pain and cognitive control are functionally segregated in distinct subdivisions of the cingulate cortex. However, recent observations encourage a fundamentally different view. Imaging studies demonstrate that negative affect, pain and cognitive control activate an overlapping region of the dorsal cingulate — the anterior midcingulate cortex (aMCC). Anatomical studies reveal that the aMCC constitutes a hub where information about reinforcers can be linked to motor centres responsible for expressing affect and executing goal-directed behaviour. Computational modelling and other kinds of evidence suggest that this intimacy reflects control processes that are common to all three domains. These observations compel a reconsideration of the dorsal cingulate's contribution to negative affect and pain.

The integration of negative affect, pain and cognitive control in the cingulate cortex

The measurement of pupil diameter in psychology (in short, "pupillometry") has just celebrated 50 years. The method established itself after the appearance of three seminal studies (Hess & Polt, 1960, 1964; Kahneman & Beatty, 1966). Since then, the method has continued to play a significant role within the field, and pupillary responses have been successfully used to provide an estimate of the "intensity" of mental activity and of changes in mental states, particularly changes in the allocation of attention and the consolidation of perception. Remarkably, pupillary responses provide a continuous measure regardless of whether the participant is aware of such changes. More recently, research in neuroscience has revealed a tight correlation between the activity of the locus coeruleus (i.e., the "hub" of the noradrenergic system) and pupillary dilation. As we discuss in this short review, these neurophysiological findings provide new important insights to the meaning of pupillary responses for mental activity. Finally, given that pupillary responses can be easily measured in a noninvasive manner, occur from birth, and can occur in the absence of voluntary, conscious processes, they constitute a very promising tool for the study of preverbal (e.g., infants) or nonverbal participants (e.g., animals, neurological patients).

Pupillometry: A Window to the Preconscious?

Diabetes mellitus (a group of metabolic disorders characterized by hyperglycemia) and periodontitis (a microbially induced inflammatory disorder that affects the supporting structures of teeth) are both common, chronic conditions. Multiple studies have demonstrated that diabetes mellitus (type 1 and type 2) is an established risk factor for periodontitis. Findings from mechanistic studies indicate that diabetes mellitus leads to a hyperinflammatory response to the periodontal microbiota and also impairs resolution of inflammation and repair, which leads to accelerated periodontal destruction. The cell surface receptor for advanced glycation end products and its ligands are expressed in the periodontium of individuals with diabetes mellitus and seem to mediate these processes. The association between the two diseases is bidirectional, as periodontitis has been reported to adversely affect glycemic control in patients with diabetes mellitus and to contribute to the development of diabetic complications. In addition, meta-analyses conclude that periodontal therapy in individuals with diabetes mellitus can result in a modest improvement of glycemic control. The effect of periodontal infections on diabetes mellitus is potentially explained by the resulting increase in levels of systemic proinflammatory mediators, which exacerbates insulin resistance. As our understanding of the relationship between diabetes mellitus and periodontitis deepens, increased patient awareness of the link between diabetes mellitus and oral health and collaboration among medical and dental professionals for the management of affected individuals become increasingly important.

Diabetes mellitus and periodontitis: a tale of two common interrelated diseases

The purpose of this systematic review was to summarize and critically appraise the results of 10 years of human laboratory research on pain and sex/gender. An electronic search strategy was designed by a medical librarian and conducted in multiple databases. A total of 172 articles published between 1998 and 2008 were retrieved, analyzed, and synthesized. The first set of results (122 articles), which is presented in this paper, examined sex difference in the perception of laboratory-induced thermal, pressure, ischemic, muscle, electrical, chemical, and visceral pain in healthy subjects. This review suggests that females (F) and males (M) have comparable thresholds for cold and ischemic pain, while pressure pain thresholds are lower in F than M. There is strong evidence that F tolerate less thermal (heat, cold) and pressure pain than M but it is not the case for tolerance to ischemic pain, which is comparable in both sexes. The majority of the studies that measured pain intensity and unpleasantness showed no sex difference in many pain modalities. In summary, 10 years of laboratory research have not been successful in producing a clear and consistent pattern of sex differences in human pain sensitivity, even with the use of deep, tonic, long-lasting stimuli, which are known to better mimic clinical pain. Whether laboratory studies in healthy subjects are the best paradigm to investigate sex differences in pain perception is open to question and should be discussed with a view to enhancing the clinical relevance of these experiments and developing new research avenues.

A systematic literature review of 10 years of research on sex/gender and experimental pain perception - part 1: are there really differences between women and men?

The locus coeruleus (LC), the major noradrenergic nucleus of the brain, gives rise to fibres innervating most structures of the neuraxis. Recent advances in neuroscience have helped to unravel the neuronal circuitry controlling a number of physiological functions in which the LC plays a central role. Two such functions are the regulation of arousal and autonomic activity, which are inseparably linked largely via the involvement of the LC. Alterations in LC activity due to physiological or pharmacological manipulations or pathological processes can lead to distinct patterns of change in arousal and autonomic function. Physiological manipulations considered here include the presentation of noxious or anxiety-provoking stimuli and extremes in ambient temperature. The modification of LC-controlled functions by drug administration is discussed in detail, including drugs which directly modify the activity of LC neurones (e.g., via autoreceptors, storage, reuptake) or have an indirect effect through modulating excitatory or inhibitory inputs. The early vulnerability of the LC to the ageing process and to neurodegenerative disease (Parkinson's and Alzheimer's diseases) is of considerable clinical significance. In general, physiological manipulations and the administration of stimulant drugs, alpha(2)-adrenoceptor antagonists and noradrenaline uptake inhibitors increase LC activity and thus cause heightened arousal and activation of the sympathetic nervous system. In contrast, the administration of sedative drugs, including alpha(2)-adrenoceptor agonists, and pathological changes in LC function in neurodegenerative disorders and ageing reduce LC activity and result in sedation and activation of the parasympathetic nervous system.

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans

Pupillary response to noxious stimulation was investigated in men (n = 11) and women (n = 9). Subjects experienced repeated trials of noxious electrical fingertip stimulation at four intensities, ranging from faint to barely tolerable pain. Measures included pupil dilation response (PDR), pain report (PR), and brain evoked potentials (EPs). The PDR began at 0.33 s and peaked at 1.25 s after the stimulus. Multivariate mixed-effects analyses revealed that (a) the PDR increased significantly in peak amplitude as stimulus intensity increased, (b) EP peaks at 150 and 250 ms differed significantly in both amplitude and latency across stimulus intensity, and (c) PR increased significantly with increasing stimulus intensity. Men demonstrated a significantly greater EP peak amplitude and peak latency at 150 ms than did women. With sex and stimulus intensity effects partialled out, the EP peak latency at 150 ms significantly predicted PR, and EP peak amplitude at 150 ms significantly predicted the PDR peak amplitude.

Phasic pupil dilation response to noxious stimulation in normal volunteers: relationship to brain evoked potentials and pain report.

Predictability of painful stimulation modulates subjective and physiological responses.

Pupil dilation response to noxious stimulation: effect of varying nitrous oxide concentration.

Background and Objective:  Several studies have shown that diabetes mellitus increases the severity of periodontitis. Conversely, periodontitis has been shown to have an impact on diabetes, although the underlying mechanisms of this are unclear. The aim of this study was to compare the inflammatory response to Porphyromonas gingivalis infection in normal and diabetic mice.



Material and Methods: Porphyromonas gingivalis were inoculated adjacent to the periosteum, at a point on the midline of the skull located between the ears, in C57BL/6 (normal) and KKAy (diabetic) mice. After induction, the levels of tumor necrosis factor-α, interleukin-6 and adiponectin in the mice were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay.



Results:  The KKAy mice showed significant increases in blood glucose, serum tumor necrosis factor-α and interleukin-6 levels after inoculation with Porphyromonas gingivalis, and a significant decrease in adiponectin to 35.7%. Similar results were observed at the mRNA level in liver and visceral adipose tissue.



Conclusion:  These observations suggest that tumor necrosis factor-α, interleukin-6 and adiponectin are an integral part of the link between diabetes mellitus and Porphyromonas gingivalis infection.

The effect of Porphyromonas gingivalis infection on cytokine levels in type 2 diabetic mice.

We investigated the temporal association between temporomandibular disorders (TMD)-related symptoms and headache during TMD treatment for patients who fulfilled the diagnostic criteria for headache attributed to TMD (HATMD) specified in the Diagnostic criteria for TMD (DC/TMD) and International classification of headache disorders (ICHD)-3 beta. The study enrolled 34 patients with HATMD induced by masticatory myofascial pain but not by temporomandibular arthralgia. Facial pain intensity, the pressure pain threshold of pericranial muscles, and maximum unassisted opening of the jaw were assessed at an initial examination and before and after physical therapy. The intensity and frequency of headache episodes and tooth contact ratio were also recorded before and after the intervention. Headache intensity and frequency significantly decreased, and these reductions were temporally related to improvements in facial pain intensity, maximum unassisted opening, and pressure pain threshold during TMD treatment. Linear regression analysis showed significant correlations between facial pain intensity and headache intensity and between tooth contact ratio and pressure pain threshold. Among patients who fulfilled the DC/TMD and ICHD-3 beta diagnostic criteria for HATMD, headache improved during TMD treatment, and the improvement was temporally related to amelioration of TMD symptoms. These findings suggest that sensitization in the central and peripheral nervous systems is responsible for HATMD. (J Oral Sci 58, 195-204, 2016).

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Shunichi Oka

Papers

Phasic pupil dilation response to noxious stimulation in normal volunteers: relationship to brain evoked potentials and pain report.

Predictability of painful stimulation modulates subjective and physiological responses.

Pupil dilation response to noxious stimulation: effect of varying nitrous oxide concentration.

The effect of Porphyromonas gingivalis infection on cytokine levels in type 2 diabetic mice.

Headache attributed to temporomandibular disorders and masticatory myofascial pain