Aya Nakae

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models.

Huggable communication medium decreases cortisol levels

Interpersonal touch is a fundamental component of social interactions because it can mitigate physical and psychological distress. To reproduce the psychological and physiological effects associated with interpersonal touch, interest is growing in introducing tactile sensations to communication devices. However, it remains unknown whether physical contact with such devices can produce objectively measurable endocrine effects like real interpersonal touching can. We directly tested this possibility by examining changes in stress hormone cortisol before and after a conversation with a huggable communication device. Participants had 15-minute conversations with a remote partner that was carried out either with a huggable human-shaped device or with a mobile phone. Our experiment revealed significant reduction in the cortisol levels for those who had conversations with the huggable device. Our approach to evaluate communication media with biological markers suggests new design directions for interpersonal communication media to improve social support systems in modern highly networked societies.

A Meta-Analysis of Hypnosis for Chronic Pain Problems: A Comparison Between Hypnosis, Standard Care, and Other Psychological Interventions

Abstract Hypnosis is regarded as an effective treatment for psychological and physical ailments. However, its efficacy as a strategy for managing chronic pain has not been assessed through meta-analytical methods. The objective of the current study was to conduct a meta-analysis to assess the efficacy of hypnosis for managing chronic pain. When compared with standard care, hypnosis provided moderate treatment benefit. Hypnosis also showed a moderate superior effect as compared to other psychological interventions for a nonheadache group. The results suggest that hypnosis is efficacious for managing chronic pain. Given that large heterogeneity among the included studies was identified, the nature of hypnosis treatment is further discussed.

5-HT2C receptor agonists attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain.

Peripheral branches of the trigeminal nerve may be damaged during maxillofacial injury or surgical procedures and trigeminal trauma may induce severe pain that is very challenging to treat. Chronic constriction injury to the infraorbital nerve (ION‐CCI) by loose ligatures has proven a useful model for some types of trigeminal neuropathic pain disorder. Using ION‐CCI rats, we examined the antiallodynic effects of intrathecally administered agents which are selective for 5‐HT2C receptors. Allodynia was evaluated by applying von Frey filaments to skin innervated by the injured ION. Dose‐dependent antiallodynic effects followed administration of three 5‐HT2C receptor agonists, 6‐chloro‐2‐(1‐piperazinyl)‐pyrazine (MK212: 10, 30, and 100 μg); (S)‐2‐(chloro‐5‐fluoro‐indol‐l‐yl)‐1‐methyamine fumarate (RO 60‐0175: 10, 30, and 100 μg); (AaR)‐8,9‐dichloro‐2,3,4,4a‐tetrahydro‐1H‐pyrazino[1,2‐a]quinoxalin‐5(6H)‐one (WAY‐161503: 10, 30, and 100 μg). ED50 values for antiallodynic effects of MK212, RO 60‐0175, and WAY‐161503 were 39.62, 46.67, and 51.22 μg, respectively. Intrathecal administration of the 5‐HT2C receptor antagonist, 8‐[5‐2,4‐dimethoxy‐5‐(4‐trifluoromethylphenylsulphonamido)phenyl‐5‐oxopentyl]‐1,3,8‐triazaspiro[4,5]decane‐2,4‐dione (RS‐102221: 30 μg) did not alter the mechanical threshold. Intrathecal pretreatment with RS‐102221 (10 and 30 μg) reduced the antiallodynic effects of the highest dose of 5‐HT2C agonists. These results indicated that, in this rat model, the 5‐HT2C receptor plays a role in spinal inhibition of trigeminal neuropathic pain.

Serotonin2C receptor mRNA editing in neuropathic pain model.

We investigated the effects on 5HT(serotonin) 2C receptor RNA editing efficiency of contusive SCI (spinal cord injury). Using cloning followed by sequence analysis on spinal cord samples taken, we compared mRNA editing. Our results might be evidence of a functional adaptation mechanism in which increased expression of 5HT2C mRNA isoforms that encode receptors more sensitive to serotonin works to activate brainstem-spinal descending 5HT systems to, in effect, suppress transmission of nociceptive signals from primary afferent neurons to the spinal dorsal horn.

Arytenoid dislocation after cardiac surgery.

Occurring most usually as complications of upper aerodigestive tract instrumentation during endotracheal intubation or extubation, arytenoid cartilage dislocation and arytenoid subluxation are uncommon laryngeal injuries. Their precise cause, however, is usually difficult to determine. We encountered arytenoid dislocation following cardiac surgery requiring the use of transesophageal echocardiography (TEE). This case prompted us to review some of the mechanisms of injury to the cricoarytenoid joint. We conclude that even very subtle force may dislocate the arytenoid cartilage. We speculate that careless insertion of a TEE probe is mechanically capable of causing arytenoid dislocation and arytenoid subluxation.

The role of RNA editing of the serotonin 2C receptor in a rat model of oro-facial neuropathic pain

We examined whether infraorbital nerve injury affected the RNA editing efficiency of the serotonin (5HT) 2C receptor in the cervical spinal cord, in association with increased pain thresholds, and whether a 5HT reuptake inhibitor (fluvoxamine; Depromel®, Meiji Seika, Tokyo, Japan) altered this editing. Accordingly, we injured rats with an infraorbital nerve loose ligation and examined the pain thresholds, mRNA and mRNA editing of the 5HT2C receptor. We evaluated changes in mRNA editing and 5HT2C mRNA expression using cloning along with sequence analysis and quantitative reverse transcription‐polymerase chain reaction to compare samples taken at post‐injury day 28 from spinal cord sites, including the trigeminal nucleus caudalis, in naive, sham and injured rats (groups of each type had also received fluvoxamine). 5HT2C receptor expression was maintained post‐injury. The RNA editing efficiency was statistically significantly lower at molecular sites A and B in ipsilateral spinal cord samples from injured rats than in bilateral samples from naive and sham rats, and in contralateral samples from injured rats. After injury, the proportional presence of two receptor isoforms changed, i.e. statistically significantly less VNV and significantly more INV and ISV. The proportions reverted after fluvoxamine administration. The post‐injury change might be evidence of a functional adaptation mechanism that increases the expression of 5HT2C mRNA isoforms that encode receptors that are more sensitive to 5HT. This would activate the brainstem–spinal descending 5HT systems and, in effect, suppress nociceptive signals from primary afferent neurons to the spinal trigeminal nucleus caudalis.

Pregnancy does not enhance volatile anesthetic sensitivity on the brain: an electroencephalographic analysis study.

Backgrounds:Parturients are thought to be more sensitive to inhalational anesthetics because their minimum alveolar concentration is decreased. However, this conventional theory may be wrong, because, according to recent animal studies, minimum alveolar concentration indicates anesthetic effect on the spinal cord but not on the brain. The aim of this electroencephalographic study was to investigate the differences in the hypnotic effect of sevoflurane on parturients and nonpregnant patients. Methods:Fifteen parturients undergoing cesarean section and 15 patients undergoing elective gynecologic surgery were enrolled. Anesthesia was induced with 4 mg/kg thiopental, 2 &mgr;g/kg fentanyl, and 2 mg/kg suxamethonium or 0.15 mg/kg vecuronium. Anesthesia was maintained with sevoflurane and fentanyl. The electroencephalographic signals, obtained from the bispectral index monitor, were recorded on a computer. We calculated 95% spectral edge frequency, amplitude, and bicoherence using custom software (Bispectrum Analyzer for bispectral index). After confirming that end-tidal sevoflurane had reached equilibrium, we measured electroencephalographic parameters of sevoflurane at 2.0 and 1.5% during surgery and at 1.0 and 0.5% after surgery. Results:With the decrease of end-tidal sevoflurane concentration from 2.0 to 0.5%, 95% spectral edge frequency, amplitude, bispectral index, and bicoherence values changed dose-dependently in pregnant and nonpregnant women (P < 0.0001). However, there were no significant differences in those electroencephalographic parameters in pregnant and nonpregnant women. Conclusions:This electroencephalographic study has shown that pregnancy does not enhance hypnotic effect of sevoflurane. These results suggested that the decrease in minimum alveolar concentration during pregnancy does not mean an enhanced volatile anesthetic effect on the brain.

Validity, Reliability, and Assessment Sensitivity of the Japanese Version of the Short-Form McGill Pain Questionnaire 2 in Japanese Patients with Neuropathic and Non-Neuropathic Pain

OBJECTIVE The objective of this study was to define the validity, reliability, and assessment sensitivity of the Japanese version of the Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2-J). DESIGN This is a cross-sectional study. PATIENTS AND METHODS The original SF-MPQ-2 was translated into Japanese to create the SF-MPQ-2-J, and the cross-cultural equivalence of assessment tool for Japanese patients was validated. The reliability of the SF-MPQ-2-J was assessed using internal consistency, reliability coefficients (Cronbachs α), and reproducibility coefficients (intraclass correlation coefficient) obtained using 234 patients with chronic pain. SF-MPQ-2-J validity was assessed based on associations identified between total and subscale scores compared with other assessment methods. A confirmatory factor analysis (CFA) was also performed to test the theoretical structure of the SF-MPQ-2-J. RESULTS The internal consistencies calculated included continuous pain, α=0.893; intermittent pain, α=0.875; predominantly neuropathic pain, α=0.917; affective descriptors, α=0.857; and total score, α=0.907. The reproducibility coefficients calculated included continuous pain, ρ=0.81; intermittent pain, ρ=0.78; predominantly neuropathic pain, ρ=0.85; affective descriptors, ρ=0.75; and total score, ρ=0.83. The CFA showed that the model fit of the readily interpretable subscales was acceptable, and the goodness of fit index value was 0.917. In addition, the mean predominantly neuropathic pain subscale score was found to be significantly higher for patients with neuropathic pain vs non-neuropathic pain. CONCLUSION These findings suggest that the reliability and validity of the SF-MPQ-2-J are excellent, and the SF-MPQ-2-J represents a cross-cultural equivalent to SF-MPQ-2. Consequently, the latter is suitable for research and clinical use, and for discriminating neuropathic pain from non-neuropathic pain.

Age-related and sex-related changes in perfusion index in response to noxious electrical stimulation in healthy subjects.

Background Even though pain is a subjective phenomenon, its objective evaluation in humans is important because subjects requiring pain evaluation may be unable to describe their pain intensity because of decreased awareness or impaired cognitive function. Previous reports indicate that the perfusion index (PI), which is calculated from pulse oximeter waveforms, has some utility in assessing pain. However, age-associated and sex-associated differences in change of PI have hitherto not been evaluated for assessment of pain. Therefore, we aimed to estimate the utility of age-related differences in PI change among healthy volunteers subjected to electrical stimulation. Methods We measured PI and pulse rate in 70 healthy volunteers exposed to gradually increasing electrical stimulation. The subjects were classified into four groups, ie, young men, young women, aged men, and aged women. Stimulation was stopped when subjects reached their pain tolerance threshold. The average PI and pulse rate were calculated 10 seconds before and after electrical stimulation and compared across the four groups. Changes in PI and pulse rate were analyzed using the paired t-test. Results The PI was significantly decreased in response to pain stimulation in young men (P<0.0001), young women (P=0.0002), and aged men (P=0.0158). However, aged women failed to show significant changes in PI before or after stimulation. The pulse rate was not significantly altered in any of the groups. Conclusion PI may be an independent parameter reflecting the perception of noxious stimuli and could be used for objective evaluation of pain perception in healthy volunteers, except when it is used for pain evaluation in elderly women.