Shunichi Oka

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

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.

Predictability of Painful Stimulation Modulates Subjective and Physiological Responses

UNLABELLED Clinical observations suggest that the perceived intensity of a painful event increases as the unpredictability of its occurrence increases. We examined the effect of varying stimulus predictability on the Somatosensory Evoked Potential (SEP), Pupil Diameter Response (PDR), Pain Report (PR), and Fear Report (FR) in 25 healthy female volunteers experiencing repeated noxious fingertip shocks. Each volunteer underwent high- and low-stimulus intensities in 4 stimulus patterns defined by stimulus sequence (SEQ) and interstimulus interval (ISI) as follows: A) serial stimulus intensity SEQ with fixed ISI; B) serial stimulus intensity SEQ with varied ISI; C) random stimulus intensity SEQ with fixed ISI; and D) random stimulus intensity SEQ with varied ISI. Results revealed that: (1) lower stimulus predictability led to higher PR and FR, greater PDR magnitude, and greater SEP amplitude; and (2) the 4 dependent measures showed the same response pattern across levels of stimulus predictability. These findings support the hypothesis that lower stimulus predictability is associated with higher reported pain and fear as well as greater physiological arousal. PERSPECTIVE Patients undergoing painful procedures experience more distress when the occurrence of a painful event is unpredictable. Poor predictability increases pain, fear, and associated physiological arousal. Maximizing the predictability of painful events may improve the quality of patient care by minimizing associated levels of pain and fear.

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

OBJECTIVE This report examines the pain-related pupil dilation response (PDR), tracking it across mixture concentrations of nitrous oxide (N(2)O) in oxygen (O(2)) and relating its variation to change in long latency somatosensory evoked potentials (SEPs) and visual analogue scale (VAS) pain report. METHODS We varied mixture concentrations of N(2)O in O(2) (0%, 10%, 30%, and 50%), measuring PDR, SEP and VAS responses to painful electrical fingertip stimulation at high and low intensities in 15 volunteers. RESULTS Mixed effect model statistical analyses revealed that: (1) PDR increased significantly with stimulus intensity and constricted significantly with mixture concentration; (2) SEP and VAS decreased significantly with increasing mixture concentration; (3) PDR correlated with SEP amplitude and VAS across mixture concentrations; (4) subjects differed significantly in: (a) baseline PDR and SEP amplitudes, (b) rate of change of these measures across mixture concentrations; and (5) VAS increased significantly with stimulus intensity and decreased significantly with mixture concentration without significant individual differences. CONCLUSIONS The findings support the hypothesis that the pain-related PDR is a complex brain-mediated response rather than a simple sympathetic reflex. SIGNIFICANCE PDR may provide a useful indicator for studying the central processing of noxious stimuli and the effects of analgesic interventions.

Contingent negative variations associated with command swallowing in humans

OBJECTIVE To clarify the role of the cerebral cortex in the swallowing movement, the difference between the waveforms of contingent negative variation (CNV) for the command swallowing and movement-related cortical potential (MRCP) obtained during the volitional swallowing task in humans was investigated. METHODS Subjects were instructed to swallow their saliva as quickly as possible in response to a sound signal 4s after the onset of a self-paced breath holding in the command swallowing task or to swallow it while holding their breath for 4s in the volitional swallowing task. RESULTS CNV and MRCP appeared at five recording areas 1.5 and 2.0s before the onset of the suprahyoid muscle activation determined by the electromyography (EMG) during the command swallowing and volitional swallowing tasks, respectively. The CNV amplitude during the command swallowing task was significantly higher than the MRCP amplitude during the volitional swallowing task (p<0.01). However, the suprahyoid muscle activities during both tasks were not significantly different (p>0.05). CONCLUSIONS These results indicated that CNV may reflect the activities of the prefrontal cortex, in addition to the supplementary motor area, suggesting that the processing of the cue to swallow activates brain areas more widely than the volitional swallowing itself. SIGNIFICANCE It is possible to clarify the cognitive functions associated with command swallowing by analyzing CNV.

Phasic Pupil Dilation Response to Noxious Stimulation

Abstract The pupil dilation response (PDR) to a painful stimulus is a subtle, event-related increase in pupil diameter that occurs following brief noxious stimulation. It varies in amplitude with increasing stimulus intensity. Two competing hypotheses for the PDR are that (1) it reflects event-related cognitive efforts largely independent of pain, such as the task demand of discriminating intensity and readying a subjective report; and (2) like the pupillary light reflex, it is a simple reflexive response. In this study 21 subjects (11 male, 10 female) experienced painful stimuli matched in subjective intensity at two sites: finger tip and ear lobe, but they produced no subjective reports. If the PDR is a product of discriminating stimulus intensity levels and forming a report, then it should be minimal or nonexistent when subjects have no choices and make no overt judgments. On the other hand, if it is primarily a simple sympathetic reflex, then onset and peak latency should be longer for finger tip than...

Alteration of the actin cytoskeleton and localisation of the α6β1 and α3 integrins during regeneration of the rat submandibular gland

OBJECTIVES Actin filaments, which are regulated by signal transduction via integrins, play important roles in the regulation of cell differentiation and polarity. The aim of this study was to assess alterations in the cytoskeleton and the localisation of integrins during regeneration of the rat submandibular gland. DESIGN After obstruction for 7 days, the regenerating glands were collected at days 0, 1, 3, 7, 14 after duct release for analysis of regeneration. Alterations in the actin filaments were examined using phalloidin, which specifically binds to filamentous actin (F-actin), and the distributions of the α6β1 and α3 integrins were examined immunohistochemically. RESULTS F-actin was strongly localised at the apical region in the intercalated ducts of normal and day-14 glands and in duct-like structures during the regenerative process. Thereafter, actin accumulated at the basement membrane in mature acinar cells. A temporo-spatial correlation was found between the apical distribution of F-actin and α3 integrin staining. Diffuse α6β1 integrin staining, which occurred at a distal site in α3 integrin-positive cells, was observed in immature cells at day 3. At day 14, α6β1 integrin was detected at the basement membrane in terminal differentiated acinar cells. CONCLUSION These findings suggest that duct-like structures have the same properties as intercalated ducts, that alterations in α3 to α6β1 integrins regulate the generation of acinar cells from duct-like structures, and that the α6β1 integrin is involved in the differentiation of acinar cells during regeneration of the rat submandibular gland.

Receptor for advanced glycation end products (RAGE)-expressing endothelial cells co-express AGE and S100 in human periapical granulomas

OBJECTIVE The engagement of the receptor for advanced glycation end products (RAGE) by AGE or S100 perturbs homeostatic mechanisms and provides a basis for cellular dysfunction in pathological situations. To assess the mechanism of vascular immune reactions in chronic periapical periodontitis, we analysed co-expression of RAGE and AGE or S100 in periapical granulomas. METHODS Surgically removed periapical lesions, which had been diagnosed as chronic periodontitis, were inspected histologically using paraffin-embedded sections stained with haematoxylin and eosin. Cryostat sections of the tissues, which were identified histologically as periapical granulomas, were then examined by double immunohistochemistry using polyclonal antibodies raised against human CD34 and monoclonal antibodies specific for human RAGE, AGE or S100. Dual-colour immunofluorescence image analysis was also performed to assess the co-expression of RAGE and AGE or RAGE and S100 by endothelial cells. RESULTS Marked expression of RAGE, AGE, and S100 by CD34(+) endothelial cells was noted. Dual-colour immunofluorescence image analysis revealed that the RAGE-expressing endothelial cells co-expressed AGE and S100; however, the number of RAGE-AGE-expressing endothelial cells was significantly higher than that of RAGE-S100-expressing endothelial cells. CONCLUSIONS Co-expression of RAGE and AGE by endothelial cells in periapical granulomas is more relevant than that of RAGE and S100. The possible engagement of RAGE and AGE may trigger cellular activation and mediate tissue injury.

Headache attributed to temporomandibular disorders and masticatory myofascial pain

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).

873 PUPIL DILATION RESPONSE TO NOXIOUS STIMULATION: EFFECT OF VARYING STIMULUS PATTERN

In this study, we aimed that hypnosis can be used as a method of pain control in pre, post surgical periods and during operation. We performed hypnosis on a cholecystectomy case who is 55 years old woman. She had a diagnosis with cholecystolithiasis and cholestasis. The patient was prepared for surgical operation by using hypnosis. This hypnosis method is called as Awareness Under Conscious Hypnosis (AUCH) contains three steps as MAYA (Making Acceptance with Your Awareness), induction and auto-hypnosis. Before or during operation no medicament was used for anesthesia and sedation. She did not feel any pain or discomfort during the incisions, tractions, cauterizations and sewing. She was painless with only hypnosis during and after operation. She was conscious, cooperative and quite happy during her surgery and sometimes she also volunteered to sing songs, tell stories. Her blood pressure was about 135/85mmHg and heart rate was 80−90/bpm during the operation duration. She was painless, very comfortable in dressing and walking and had no restriction in her movements after operation. This condition continued while she was staying at the hospital. She well cured and went home in 40 hours whereas the usual curing time is about 4 days for this kind of operations. As it is seen in this case, hypnosis can be used as a reliable and effective method for pain control in surgical operations. This makes us eager to study on hypnosis in pain control.