Predictors of high-cost patients with acute whiplash-associated disorder in Japan.

INTRODUCTION: The proportion of neck injuries due to traffic accidents is increasing. Little is known about high-cost patients with acute whiplash-associated disorder (WAD). The present study aimed to investigate whether time to first visit for conventional medicine, multiple doctor visits, or alternative medicine could predict high-cost patients with acute WAD in Japan. METHODS: Data from a compulsory, no-fault, government automobile liability insurance agency in Japan between 2014 and 2019 were used. The primary economic outcome was the total cost of healthcare per person. Treatment-related variables were assessed based on the time to first visit for conventional and alternative medicine, multiple doctor visits, and visits for alternative medicine. Patients were categorized according to total healthcare cost (low, medium, and high cost). The variables were subjected to univariate and multivariate analysis to compare high-cost and low-cost patients. RESULTS: A total of 104,911 participants with a median age of 42 years were analyzed. The median total healthcare cost per person was 67,366 yen. The cost for consecutive medicine, for consecutive and alternative medicine, and total healthcare costs were significantly associated with all clinical outcomes. Female sex, being a homemaker, a history of WAD claim, residential area, patient responsibility in a traffic accident, multiple doctor visits, and visits for alternative medicine were identified as independent predictive factors for a high cost in multivariate analysis. Multiple doctor visits and visits for alternative medicine showed large differences between groups (odds ratios 2673 and 694, respectively). Patients with multiple doctor visits and visits for alternative medicine showed a significantly high total healthcare cost per person (292,346 yen) compared to those without (53,587 yen). CONCLUSIONS: A high total healthcare cost is strongly associated with multiple doctor visits and visits for alternative medicine in patients with acute WAD in Japan.

Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP.

Conditions that resemble osteoarthritis (OA) were produced by injection of sodium monoiodoacetate (MIA) into the knee joints of mice. Bone marrow derived mast cells (BMMCs) injected into the OA knee joints enhanced spontaneous pain. Since no spontaneous pain was observed when BMMCs were injected into the knee joints of control mice that had not been treated with MIA, BMMCs should be activated within the OA knee joints and release some pain-inducible factors. Protease activated receptor-2 (PAR2) antagonist (FSLLRY-NH2) almost abolished the pain-enhancing effects of BMMCs injected into the OA knee joints, suggesting that tryptase, a mast cell protease that is capable of activating PAR2, should be released from the injected BMMCs and enhance pain through activation of PAR2. When PAR2 agonist (SLIGKV-NH2) instead of BMMCs was injected into the OA knee joints, it was also enhanced pain. Apyrase, an ATP degrading enzyme, injected into the OA knee joints before BMMCs suppressed the pain enhanced by BMMCs. We showed that purinoceptors (P2X4 and P2X7) were expressed in BMMCs and that extracellular ATP stimulated the release of tryptase from BMMCs. These observations suggest that ATP may stimulate degranulation of BMMCs and thereby enhanced pain. BMMCs injected into the OA knee joints stimulated expression of IL-1ß, IL-6, TNF-α, CCL2, and MMP9 genes in the infrapatellar fat pads, and PAR2 antagonist suppressed the stimulatory effects of BMMCs. Our study suggests that intermittent pain frequently observed in OA knee joints may be due, at least partly, to mast cells through activation of PAR2 and action of ATP, and that intraarticular injection of BMMCs into the OA knee joints may provide a useful experimental system for investigating molecular mechanisms by which pain is induced in OA knee joints.

The acoustic startle reflex as a tool for assessment of odor environment effects on affective states in laboratory mice.

Apart from self and conspecific odors, odors from other species also influence the affective states in laboratory mice (Mus musculus musculus) in their home cages and during experimental procedures, possibly inducing confusion and inconsistency in experimental data. Thus, it is important to detect the types of animal odors associated with housing, husbandry, and laboratory practice that can arouse different types of affective changes in mice. Here, we aimed to test the effectiveness of the acoustic startle reflex (ASR) in detecting changes in the affective states of laboratory mice due to animal-derived-odor as it has a non-zero baseline, and can be enhanced or attenuated by positive or negative affective shifts, respectively. We used ASR to examine the affective changes in mice that were induced by bedding odors and an alarm pheromone. The odor of bedding obtained from the mice' home cages significantly attenuated the ASR, suggesting positive affective shifts in the test mice, whereas that from bedding obtained from rat cages significantly enhanced the ASR, suggesting negative affective shifts. No significant changes in ASR were observed in mice presented with the odor of bedding obtained from cages of unfamiliar conspecifics. In contrast, there was significant ASR enhancement in mice exposed to volatile components of alarm pheromones trapped in water, suggesting negative affective shifts. Thus, our findings show that ASR may be a valuable tool in assessing the effects of odors on the affective states in laboratory mice.

Effects of Virtual Reality-Based Exercise Imagery on Pain in Healthy Individuals.

OBJECTIVE: Virtual reality (VR) is an advanced technology that can be used to attenuate pain. The present study aimed to investigate which method was more effective for pain management: VR combined with exercise imagery or VR distraction. METHODS: Fifty-two healthy students participated in this randomized cross-over controlled trial. One VR-based task aimed to passively use the imagery of driving a car as a distraction intervention (the driving group), whereas the other VR-based task aimed to use exercise imagery (running) to actively engage the participants in movement (the running group). The mechanical pressure pain thresholds of the quadriceps and forearm and the heat pain threshold of the hand of each subject were measured before, during, and after each VR task. The differences between the values at each time point and the differences between the groups were analyzed. RESULTS: The pressure and heat pain thresholds were significantly greater during VR task than those before VR task in both driving and running groups. The changes in the pressure pain thresholds that occurred during VR task were significantly higher in the running group than in the driving group. The difference between groups gradually declined after VR task. Conversely, there was no significant difference in the changes in the heat pain thresholds between the groups both during VR task and after VR task. CONCLUSIONS: VR combined with exercise imagery has a greater effect on pressure pain thresholds, but not heat pain thresholds, than VR distraction.

Changes in acoustic startle reflex in rats induced by playback of 22-kHz calls.

In aversive or dangerous situations, adult rats emit long characteristic ultrasonic calls, often termed "22-kHz calls," which have been suggested to play a role of alarm calls. Although the playback experiment is one of the most effective ways to investigate the alarming properties of 22-kHz calls, clear behavioral evidence showing the anxiogenic effects of these playback stimuli has not been directly obtained to date. In this study, we investigated whether playback of 22-kHz calls or synthesized sine tones could change the acoustic startle reflex (ASR), enhancement of which is widely considered to be a reliable index of anxiety-related negative affective states in rats. Playback of 22-kHz calls significantly enhanced the ASR in rats. Enhancement effects caused by playback of 22-kHz calls from young rats were relatively weak compared to those after calls from adult rats. Playback of synthesized 25-kHz sine tones enhanced ASR in subjects, but not synthesized 60-kHz tones. Further, shortening the individual call duration of synthesized 25-kHz sine tones also enhanced the ASR. Accordingly, it is suggested that 22-kHz calls induce anxiety by socially communicated alarming signals in rats. The results also demonstrated that call frequency, i.e., of 22kHz, appears important for ultrasonic alarm-signal communication in rats.

Effects of Kamishoyosan, a Traditional Japanese Kampo Medicine, on Pain Conditions in Patients with Intractable Persistent Dentoalveolar Pain Disorder.

There are patients who suffer from persistent dentoalveolar pain disorder (PDAP) which is a pain of the teeth, either dentoalveolar pain or nonodontogenic toothache, and its cause has not yet been identified. An effective intervention for PDAP has not yet been established. Interventions for patients with PDAP are generally pharmacological treatments such as antidepressants, anticonvulsants, and pregabalin. However, these medicines are not always effective for patients. The pain disorder in the orofacial region including temporomandibular disorder (TMD) and PDAP was effectively treated with our original exercise therapy. However, we did observe some intractable cases of PDAP even when our original exercise therapy was used. This paper presents our findings in which Kamishoyosan improved the pain intensity in 14 out of 15 PDAP patients refractory to our original exercise therapy.

Echoic memory: investigation of its temporal resolution by auditory offset cortical responses.

Previous studies showed that the amplitude and latency of the auditory offset cortical response depended on the history of the sound, which implicated the involvement of echoic memory in shaping a response. When a brief sound was repeated, the latency of the offset response depended precisely on the frequency of the repeat, indicating that the brain recognized the timing of the offset by using information on the repeat frequency stored in memory. In the present study, we investigated the temporal resolution of sensory storage by measuring auditory offset responses with magnetoencephalography (MEG). The offset of a train of clicks for 1 s elicited a clear magnetic response at approximately 60 ms (Off-P50m). The latency of Off-P50m depended on the inter-stimulus interval (ISI) of the click train, which was the longest at 40 ms (25 Hz) and became shorter with shorter ISIs (2.5∼20 ms). The correlation coefficient r2 for the peak latency and ISI was as high as 0.99, which suggested that sensory storage for the stimulation frequency accurately determined the Off-P50m latency. Statistical analysis revealed that the latency of all pairs, except for that between 200 and 400 Hz, was significantly different, indicating the very high temporal resolution of sensory storage at approximately 5 ms.

The review of innovative integration of Kampo medicine and Western medicine as personalized medicine at the first multidisciplinary pain center in Japan.

BACKGROUND: The Japanese medical system is unique because it is the only country in the world where Western medicine and traditional Japanese medicine including Kampo medicine, traditional Japanese herbal medicine, are used in our daily clinical practice. Pain is essentially an interactive psychophysiological behavior pattern. Thus, an interdisciplinary approach is often recommended in providing appropriate therapeutic care for the patients suffering from chronic and intractable pain. In addition, we have been prescribing Kampo medicines in combination with Western medicines as personalized medicine in order to treat patients with chronic pain at our pain center. The aim of our study was to conduct a survey on the current use and the effect of Kampo medicines in our multidisciplinary pain center. METHODS: Retrospective analysis was performed on 221 out of 487 patients suffering from chronic pain. RESULTS: The most frequent medical complaints for which Kampo medicines were prescribed were lower back/lower limb pain, neck/upper limb pain, various facial pains, headache/migraine, whiplash-associated disorder, and frozen shoulder. Kampo medicines were prescribed based on patient-centered Kampo diagnosis. Moreover, several Kampo medicines generally for the management of psychological symptoms were prescribed for about 70% of the patients. Pain improvement in the patients was categorized as follows: 26.3% with marked improvement, 12.7% with moderate improvement, 38.9% with some improvement, and 19.9% with no improvement. CONCLUSIONS: Two thirds of the chronic pain patients with the use of Kampo medicines combined with Western medicine experienced further pain improvements.

Distal traditional acupuncture points of the large intestinal meridian and the stomach meridian differently affect heart rate variability and oxygenation of the trapezius muscle.

Physicians in traditional Chinese medicine have found that acupoints and meridians have effects on specific parts of the body. The aim of this study was to see how acupressure at distal acupuncture points of a specific meridian affects heart rate variability (HRV) and oxygenation of the trapezius muscle. Forty-one female participants were randomly allocated to three groups. Subjects in the Stomach Meridian acupuncture point (ST) group received acupressure at ST 34, ST 36, and ST 41, subjects in the Large Intestinal Meridian acupuncture point (LI) group received acupressure at LI 4, LI 10, and LI 11, and subjects in the control group did not receive any stimuli. HRV and oxygenation of the trapezius muscles were measured. The high frequency components of HRV in the control and LI groups tended to be higher than those in the ST group. Total hemoglobin in the control and LI groups eventually reached significantly higher levels than in the ST group. While oxyhemoglobin (ΔO2Hb) in the control and LI groups did not change, ΔO2Hb in the ST significantly decreased temporarily.

Transcutaneous Electrical Nerve Stimulation on the PC-5 and PC-6 Points Alleviated Hypotension after Epidural Anaesthesia, Depending on the Stimulus Frequency.

Neuraxial blockade causes arterial hypotension. Transcutaneous electrical nerve stimulation (TENS) at the Neiguan (PC-6) and Jianshi (PC-5) reduces the severity of hypotension after spinal anaesthesia, but did not clarify the optimal stimulus frequency. We hypothesized that the stimulus frequency of TENS at the PC-6 and PC-5 points would influence the severity of hypotension after epidural anaesthesia. 65 ASA I or II male patients presenting for inguinal hernia repair were randomized to five groups: the control group received no treatment; the 2 Hz, 10 Hz, 20 Hz, and 40 Hz groups received TENS at a frequency of 2 Hz, 10 Hz, 20 Hz, and 40 Hz, respectively. The lowest SBP was significantly higher in the 40 Hz group [the control, 84 (74-110) mmHg; the 2 Hz, 96 (62-116) mmHg; the 10 Hz, 100 (68-110) mmHg; the 20 Hz, 96 (64-115) mmHg; the 40 Hz, 104 (75-140) mmHg: P = 0.004]. Significantly less patients experienced hypotension in the 40 Hz group [the control, 78%; the 2 Hz, 43%; the 10 Hz, 38%; the 20 Hz, 38%; the 40 Hz, 8%: P = 0.008]. TENS on the PC-6 and PC-5 points reduced the severity and incidence of hypotension after epidural anaesthesia, depending on the stimulus frequency.

Prevalence and characteristics of chronic musculoskeletal pain in Japan.

BACKGROUND: This cross-sectional study was conducted to obtain epidemiologic data on chronic musculoskeletal pain in the Japanese people, and with it a better understanding of the actual conditions and problems involved. METHODS: A questionnaire covering basic information, chronic musculoskeletal pain, daily life, quality of life, and social loss was prepared and mailed to 11507 individuals aged 18 years or older. Subjects were selected randomly nationwide in accordance with the demographic composition of Japan. RESULTS: The prevalence of chronic musculoskeletal pain was 15.4%. The prevalence was highest in people in their 30s to 50s. Pain occurred most frequently in the low back, neck, shoulder, and knee. Among symptomatic subjects, 42% sought treatment, by visiting a medical institution (19%), taking folk remedies (20%), or both (3%). Treatment was generally prolonged, with 70% of those treated reporting treatment durations of more than a year. Although 69% reported that their symptoms had improved, 30% reported unchanged or aggravated symptoms and dissatisfaction with treatment. Among symptomatic subjects, a high percentage of both men and women had lost jobs, left school, been absent from work or school, or had changed jobs. Basic activities of daily living (ADL) were disturbed in men, and the instrumental ADL (IADL) score was low in women. SF-36 scale scores were significantly lower in every area for subjects with chronic pain. CONCLUSIONS: Chronic musculoskeletal pain does not necessarily improve even with prolonged treatment. It adversely affects daily life and both physical and mental health. Because those suffering pain often increasingly need assistance in daily activities, people around them are also affected. The therapeutic system and treatment procedures for chronic musculoskeletal pain merit prompt review.

Comparative effects of acupressure at local and distal acupuncture points on pain conditions and autonomic function in females with chronic neck pain.

Acupressure on local and distal acupuncture points might result in sedation and relaxation, thereby reducing chronic neck pain. The aim was to investigate the effect of acupressure at local (LP) and distal acupuncture points (DP) in females with chronic neck pain. Thirty-three females were assigned to three groups: the control group did not receive any stimuli, the LP group received acupressure at local acupuncture points, GB 21, SI 14 and SI 15, and the DP group received acupressure at distal acupuncture points, LI 4, LI 10 and LI 11. Verbal rating scale (VRS), Neck Disability Index (NDI), State-Trait Anxiety Inventory (STAI), muscle hardness (MH), salivary alpha-amylase (sAA) activity, heart rate (HR), heart rate variability (HRV) values and satisfaction due to acupressure were assessed. VRS, NDI, STAI and MH values decreased after acupressure in the LP and the DP group. HR decreased and the power of high frequency (HF) component of HRV increased after acupressure in only the LP group. Although acupressure on not only the LP but also the DP significantly improved pain conditions, acupressure on only the LP affected the autonomic nervous system while acupuncture points per se have different physical effects according to location.

The Influence of Acupressure at Extra 1 Acupuncture Point on the Spectral Entropy of the EEG and the LF/HF Ratio of Heart Rate Variability.

Acupressure applied on the Extra 1 acupuncture point results in sedation, thereby reducing bispectral index (BIS) values. Mental status and hypnotic agents influence the autonomic nervous system. We hypothesized that acupressure at the Extra 1 point would induce sedation and change sympatho-parasympathetic nerve balance. We investigated the effect of acupressure at the Extra 1 point on the EEG spectral entropy values and heart rate variability (HRV). Forty-eight volunteers (24 males and 24 females) were randomly assigned to the control or Extra 1 group. The control group received acupressure at a sham point and the Extra 1 group received acupressure at the Extra 1 point. Acupressure was applied for 5 min. The record of the EEG spectral entropy values and HRV started 5 min before acupressure and stopped 5 min after acupressure. Acupressure significantly reduced the EEG spectral entropy values in both groups, but the values of the Extra 1 group were significantly smaller than those of the control group (P < .01). Acupressure significantly decreased the LF/HF ratio of HRV in both groups (P < .05). When divided upon gender, although acupressure tended to decrease the LF/HF ratio, the ratio significantly decreased during and after acupressure only in females of the Extra 1 group (P < .05). We concluded that acupressure on the Extra 1 point significantly reduced the EEG spectral entropy in both the genders, but affected the LF/HF ratio of HRV only in females.

Low-dose gabapentin as useful adjuvant to opioids for neuropathic cancer pain when combined with low-dose imipramine.

PURPOSE: Painful neuropathic conditions of cancer pain often show little response to nonopioid and opioid analgesics but may be eased by antidepressants and anticonvulsants. Although gabapentin is effective in the treatment of neuropathic pain in patients with cancer, some patients experience intolerable side effects sufficient to warrant discontinuation. The aim of this study was to see whether low-dose gabapentin is effective in treating cancer-related neuropathic pain when combined with low-dose imipramine. METHODS: Fifty-two cancer patients diagnosed as having neuropathic pain were allocated into four groups: G400-I group took gabapentin 200 mg and imipramine 10 mg every 12 h orally; G400 group took gabapentin 200 mg every 12 h orally; G800 group took gabapentin 400 mg every 12 h orally; I group took imipramine 10 mg every 12 h orally. RESULTS: Low-dose gabapentin-imipramine significantly decreased the total pain score and daily paroxysmal pain episodes. Several patients developed mild adverse symptoms in the four groups, and three patients discontinued treatment due to severe adverse events in the G800 group. CONCLUSION: Low-dose gabapentin-antidepressant combination with opioids was effective in managing neuropathic cancer pain without severe adverse effects.

The effect of acupressure at the extra 1 point on subjective and autonomic responses to needle insertion.

BACKGROUND: Premedication with sedatives can decrease the discomfort associated with invasive anesthetic procedures. Some researchers have shown that acupressure on the acupuncture extra 1 point is effective for sedation. We investigated whether acupressure on the extra 1 point could alleviate the pain of needle insertion. METHODS: We investigated the effect of acupressure at the extra 1 point or a sham point on needle insertion using verbal rating scale (VRS) pain scores and heart rate variability (HRV). Twenty-two healthy female volunteers were randomly allocated to two groups: the extra 1 group received acupressure at the extra 1 point, and the sham group received acupressure at a sham point. After starting the electrocardiogram record, a 27-gauge needle was inserted into the skin of a forearm. Thereafter, another needle was inserted into the skin of the other forearm during acupressure. RESULTS: Acupressure at the extra 1 point significantly reduced the VRS, but acupressure at the sham increased the VRS. Acupressure at the extra 1 significantly reduced the low frequency/high frequency ratio of HRV responding to needle insertion. CONCLUSIONS: Acupressure at the extra 1 point significantly reduced needle insertion pain compared with acupressure at the sham point. Also, acupressure at the extra 1 point significantly reduced the low frequency/high frequency ratio of HRV responding to needle insertion, which implies a reduction in sympathetic nervous system activity.