Processing of sensory, painful and vestibular stimuli in the thalamus.

OBJECTIVES: The thalamus plays an important role in the mediation and integration of various stimuli (e.g., somatosensory, pain, and vestibular). Whether a stimulus-specific and topographic organization of the thalamic nuclei exists is still unknown. The aim of our study was to define a functional, in vivo map of multimodal sensory processing within the human thalamus. METHODS: Twenty healthy individuals (10 women, 21-34 years old) participated. Defined sensory stimuli were applied to both hands (innocuous touch, mechanical pain, and heat pain) and the vestibular organ (galvanic stimulation) during 3 T functional MRI. RESULTS: Bilateral thalamic activations could be detected for touch, mechanical pain, and vestibular stimulation within the left medio-dorsal and right anterior thalamus. Heat pain did not lead to thalamic activation at all. Stimuli applied to the left body side resulted in stronger activation patterns. Comparing an early with a late stimulation interval, the mentioned activation patterns were far more pronounced within the early stimulation interval. CONCLUSIONS: The right anterior and ventral-anterior nucleus and the left medio-dorsal nucleus appear to be important for the processing of multimodal sensory information. In addition, galvanic stimulation is processed more laterally compared to mechanical pain. The observed changes in activity within the thalamic nuclei depending on the stimulation interval suggest that the stimuli are processed in a thalamic network rather than a distinct nucleus. In particular, the vestibular network within the thalamus recruits bilateral nuclei, rendering the thalamus an important integrative structure for vestibular function.

Effect of Virtual Reality Hypnosis on Pain Threshold and Neurophysiological and Autonomic Biomarkers in Healthy Volunteers: Prospective Randomized Crossover Study.

BACKGROUND: Virtual reality hypnosis (VRH) is a promising tool to reduce pain. However, the benefits of VRH on pain perception and on the physiological expression of pain require further investigation. OBJECTIVE: In this study, we characterized the effects of VRH on the heat pain threshold among adult healthy volunteers while monitoring several physiological and autonomic functions. METHODS: Sixty healthy volunteers were prospectively included to receive nociceptive stimulations. The first set of thermal stimuli consisted of 20 stimulations at 60°C (duration 500 milliseconds) to trigger contact heat evoked potentials (CHEPs). The second set of thermal stimuli consisted of ramps (1°C/second) to determine the heat pain threshold of the participants. Electrocardiogram, skin conductance responses, respiration rate, as well as the analgesia nociception index were also recorded throughout the experiment. RESULTS: Data from 58 participants were analyzed. There was a small but significant increase in pain threshold in VRH (50.19°C, SD 1.98°C) compared to that in the control condition (mean 49.45°C, SD 1.87; P<.001, Wilcoxon matched-pairs signed-rank test; Cohen d=0.38). No significant effect of VRH on CHEPs and heart rate variability parameters was observed (all P>0.5; n=22 and n=52, respectively). During VRH, participants exhibited a clear reduction in their autonomic sympathetic tone, as shown by the lower number of nonspecific skin conductance peak responses (P<.001, two-way analysis of variance; n=39) and by an increase in the analgesia nociception index (P<.001, paired t-test; n=40). CONCLUSIONS: The results obtained in this study support the idea that VRH administration is effective at increasing heat pain thresholds and impacts autonomic functions among healthy volunteers. As a nonpharmacological intervention, VRH has beneficial action on acute experimental heat pain. This beneficial action will need to be evaluated for the treatment of other types of pain, including chronic pain.

Neural mechanisms of pain processing differ between endurance athletes and nonathletes: A functional connectivity magnetic resonance imaging study.

Pain perception and the ability to modulate arising pain vary tremendously between individuals. It has been shown that endurance athletes possess higher pain tolerance thresholds and a greater effect of conditioned pain modulation than nonathletes, both indicating a more efficient system of endogenous pain inhibition. The aim of the present study was to focus on the neural mechanisms of pain processing in endurance athletes that have not been investigated yet. Therefore, we analyzed the pain processing of 18 male athletes and 19 healthy male nonathletes using functional magnetic resonance imaging. We found lower pain ratings in endurance athletes compared to nonathletes to physically identical painful stimulation. Furthermore, brain activations of athletes versus nonathletes during painful heat stimulation revealed reduced activation in several brain regions that are typically activated by nociceptive stimulation. This included the thalamus, primary and secondary somatosensory cortex, insula, anterior cingulate cortex, midcingulate cortex, dorsolateral prefrontal cortex, and brain stem (BS). Functional connectivity analyses revealed stronger network during painful heat stimulation in athletes between the analyzed brain regions except for connections with the BS that showed reduced functional connectivity in athletes. Post hoc correlation analyses revealed associations of the subject's fitness level and the brain activation strengths, subject's fitness level and functional connectivity, and brain activation strengths and functional connectivity. Together, our results demonstrate for the first time that endurance athletes do not only differ in behavioral variables compared to nonathletes, but also in the neural processing of pain elicited by noxious heat.

Essential oil inhaler (AromaStick®) improves heat tolerance in the Hot Immersion Test (HIT). Results from two randomized, controlled experiments.

BACKGROUND: A recent review article on an aromatherapeutic inhaler demonstrated clinical effects on a number of bodily systems, like the cardiovascular system, the respiratory system, the nervous system and the endocrine system. OBJECTIVE: This paper extends these findings and investigates whether specially designed essential oils inhalers are capable to counter experimentally induced stressful heat sensations. METHOD: Two prospective, randomized, controlled experiments using the Hot Immersion Test Paradigm (HIT) were conducted to investigate whether deep odor inhalations increase heat tolerance. RESULTS: In both experiments, the inhaler strongly prolonged pain tolerance and increased blood oxygenation (1 < d < 1.3). In the second experiment, the inhaler also increased heart rate variability (d = 1.3) as a mechanism to cope with heat stress. CONCLUSION: The ability to resist a stressful thermal stimulus can be exogenously improved by short and deep inhalations of essential scents directly delivered to the olfactory system.

Local and Systemic Analgesic Effects of Nerve-Specific Acupuncture in Healthy Adults, Measured by Quantitative Sensory Testing.

OBJECTIVE: This study aims to assess whether acupuncture analgesia's effects are local or systemic and whether there is a dose response for these effects. METHODS: Twenty-eight healthy volunteers aged 18-45 were randomized to two doses of acupuncture using points closely associated with peripheral nerves in the legs. The lower-dose group involved acupoints overlying the deep peroneal nerve (DP), and the higher-dose involved acupoints overlying the deep peroneal and posterior tibial nerves (DPTN). Baseline and acupuncture quantitative sensory testing (QST) assessments were obtained locally in the calf and great toe and systemically in the hand. Results were analyzed using factorial repeated-measures analysis of variance for each of the QST variables-cold detection threshold (CDT), vibration detection threshold (VDT), heat pain threshold (HP0.5), and heat pain perception of 5/10 (HP5.0). Location (leg/hand) and time (baseline/acupuncture) were within-subject factors. Intervention (DP/DPTN) was a between-subject factor. RESULTS: CDT was increased in the calf (P < 0.001) and in the hand (P < 0.001). VDT was increased in the toe (P < 0.001) but not in the hand. HP0.5 was increased in the calf (P < 0.001) and in the hand (P < 0.001). HP5.0 was increased in the calf (P = 0.002) and in the hand (P < 0.001), with the local effect being significantly greater than the systemic (P = 0.004). In all of the above QST modalities, there was no difference between the low-dose (DP) and high-dose (DPTN) acupuncture groups. CONCLUSIONS: Acupuncture caused comparable local and systemic analgesic effects in cold detection and heat pain perception and only local effects in vibration perception. There was no clear acupuncture dose response to these effects.

[Analysis on the temperature-time curve in warm needling manipulation with acupuncture needles of different materials].

OBJECTIVE: To analyze the characteristics of the temperature-time curve in warm needling manipulation with the acupuncture needles made of copper, silver, gold and stainless steel and explore the applicable temperature range and most suitable needle materials of warm needling manipulation in clinical practice. METHODS: A total of 10 healthy subjects were included. Using the digital thermometer, with different moxibustion dose (1.2 g or 1.5 g, moxa), the temperature was measured at the site where the skin contacts with the needle body during the warm needling manipulation with stainless steel needle, copper needle, gold needle and sliver needle separately. The initial heat pain threshold (the temperature when hot feeling started) and the burning pain threshold (feeling very hot but tolerable) were recorded when using the different needles mentioned above. Through the subject questionnaire, the comfort degree, the heat sensation, the adverse reaction and the acceptability to warm needling manipulation with the different needles were investigated. RESULTS: During the warm needling manipulation, the initial heat pain threshold was (42.8±2.7) ℃ and the burning pain threshold was (46.7±2.9) ℃. The strongest warm stimulation was presented in the warm needling manipulation with 1.5 g moxa and silver needle and the highest temperature was (55.5±6.3) ℃, followed by (52.9±4.2) ℃ with 1.2 g moxa and silver needle, (46.6±3.7) ℃ with 1.5 g moxa and gold needle, (46.6±1.9) ℃ with 1.5 g moxa and copper needle, (43.1±1.5) ℃ with 1.2 g moxa and copper needle and (41.7±0.9) ℃ with 1.5 g moxa and stainless steel needle. The sequence of the maintaining time of the initial heat pain threshold over 43℃ was 480 s with silver needle and 1.5 moxa, 325 s with silver needle and 1.2 g moxa, 270 s with gold needle and 1.5 g moxa, 185 s with copper needle and 1.5 g moxa, 42 s with copper needle and 1.2 g moxa and 0 s with stainless steel needle and 1.5 g moxa successively. The heat score graded by the subjects to the warm needling manipulation with different needles, from high to low, was presented in the manipulation with 1.5 g moxa and silver needle, 1.2 g moxa and silver needle, 1.5 g moxa and copper needle, 1.5 g moxa and gold needle, 1.2 g moxa and copper needle and 1.5 g moxa and stainless steel needle. The VAS score was different significantly in comparison among the six needles in warm needling manipulation (P<0.001). The comfort degree of the subjects in the warm needling manipulation with silver needle and 1.5 g moxa was significantly lower than the warm needling manipulation with the other 5 materials (P<0.05). Three subjects complained that the warm needling manipulation with silver needle and 1.5 g moxa was too hot to be tolerable and the most of subjects were willing to accept warm needling manipulation with these 6 materials (acceptability 70.0% to 100.0%). Except blisters presented in 9 subjects after warm needling manipulation with silver needle and 1.5 g moxa, no severe adverse reaction occurred in warm needling manipulation with 6 materials. CONCLUSION: In the warm needling manipulation in the human body, the initial heat pain and the burning pain threshold were 43 ℃ and 47 ℃ respectively, which is the applicable temperature range of moxibustion in clinical practice. The warm needling manipulation with silver needle induces a quite strong heat stimulation and the discomfort may be caused when the temperature is exceeded to some threshold. The warm needling manipulation with copper needle generates the onset temperature, without inducing adverse reactions, e.g. discomfort and burning in the subjects.

Analysis on the temperature-time curve in warm needling manipulation with acupuncture needles of different materials / 中国针灸

OBJECTIVE@#To analyze the characteristics of the temperature-time curve in warm needling manipulation with the acupuncture needles made of copper, silver, gold and stainless steel and explore the applicable temperature range and most suitable needle materials of warm needling manipulation in clinical practice.@*METHODS@#A total of 10 healthy subjects were included. Using the digital thermometer, with different moxibustion dose (1.2 g or 1.5 g, moxa), the temperature was measured at the site where the skin contacts with the needle body during the warm needling manipulation with stainless steel needle, copper needle, gold needle and sliver needle separately. The initial heat pain threshold (the temperature when hot feeling started) and the burning pain threshold (feeling very hot but tolerable) were recorded when using the different needles mentioned above. Through the subject questionnaire, the comfort degree, the heat sensation, the adverse reaction and the acceptability to warm needling manipulation with the different needles were investigated.@*RESULTS@#During the warm needling manipulation, the initial heat pain threshold was (42.8±2.7) ℃ and the burning pain threshold was (46.7±2.9) ℃. The strongest warm stimulation was presented in the warm needling manipulation with 1.5 g moxa and silver needle and the highest temperature was (55.5±6.3) ℃, followed by (52.9±4.2) ℃ with 1.2 g moxa and silver needle, (46.6±3.7) ℃ with 1.5 g moxa and gold needle, (46.6±1.9) ℃ with 1.5 g moxa and copper needle, (43.1±1.5) ℃ with 1.2 g moxa and copper needle and (41.7±0.9) ℃ with 1.5 g moxa and stainless steel needle. The sequence of the maintaining time of the initial heat pain threshold over 43℃ was 480 s with silver needle and 1.5 moxa, 325 s with silver needle and 1.2 g moxa, 270 s with gold needle and 1.5 g moxa, 185 s with copper needle and 1.5 g moxa, 42 s with copper needle and 1.2 g moxa and 0 s with stainless steel needle and 1.5 g moxa successively. The heat score graded by the subjects to the warm needling manipulation with different needles, from high to low, was presented in the manipulation with 1.5 g moxa and silver needle, 1.2 g moxa and silver needle, 1.5 g moxa and copper needle, 1.5 g moxa and gold needle, 1.2 g moxa and copper needle and 1.5 g moxa and stainless steel needle. The VAS score was different significantly in comparison among the six needles in warm needling manipulation (<0.001). The comfort degree of the subjects in the warm needling manipulation with silver needle and 1.5 g moxa was significantly lower than the warm needling manipulation with the other 5 materials (<0.05). Three subjects complained that the warm needling manipulation with silver needle and 1.5 g moxa was too hot to be tolerable and the most of subjects were willing to accept warm needling manipulation with these 6 materials (acceptability 70.0% to 100.0%). Except blisters presented in 9 subjects after warm needling manipulation with silver needle and 1.5 g moxa, no severe adverse reaction occurred in warm needling manipulation with 6 materials.@*CONCLUSION@#In the warm needling manipulation in the human body, the initial heat pain and the burning pain threshold were 43 ℃ and 47 ℃ respectively, which is the applicable temperature range of moxibustion in clinical practice. The warm needling manipulation with silver needle induces a quite strong heat stimulation and the discomfort may be caused when the temperature is exceeded to some threshold. The warm needling manipulation with copper needle generates the onset temperature, without inducing adverse reactions, e.g. discomfort and burning in the subjects.

Visceral and somatic pain modalities reveal NaV 1.7-independent visceral nociceptive pathways.

KEY POINTS: Voltage-gated sodium channels play a fundamental role in determining neuronal excitability. Specifically, voltage-gated sodium channel subtype NaV 1.7 is required for sensing acute and inflammatory somatic pain in mice and humans but its significance in pain originating from the viscera is unknown. Using comparative behavioural models evoking somatic and visceral pain pathways, we identify the requirement for NaV 1.7 in regulating somatic (noxious heat pain threshold) but not in visceral pain signalling. These results enable us to better understand the mechanisms underlying the transduction of noxious stimuli from the viscera, suggest that the investigation of pain pathways should be undertaken in a modality-specific manner and help to direct drug discovery efforts towards novel visceral analgesics. ABSTRACT: Voltage-gated sodium channel NaV 1.7 is required for acute and inflammatory pain in mice and humans but its significance for visceral pain is unknown. Here we examine the role of NaV 1.7 in visceral pain processing and the development of referred hyperalgesia using a conditional nociceptor-specific NaV 1.7 knockout mouse (NaV 1.7Nav1.8 ) and selective small-molecule NaV 1.7 antagonist PF-5198007. NaV 1.7Nav1.8 mice showed normal nociceptive behaviours in response to intracolonic application of either capsaicin or mustard oil, stimuli known to evoke sustained nociceptor activity and sensitization following tissue damage, respectively. Normal responses following induction of cystitis by cyclophosphamide were also observed in both NaV 1.7Nav1.8 and littermate controls. Loss, or blockade, of NaV 1.7 did not affect afferent responses to noxious mechanical and chemical stimuli in nerve-gut preparations in mouse, or following antagonism of NaV 1.7 in resected human appendix stimulated by noxious distending pressures. However, expression analysis of voltage-gated sodium channel α subunits revealed NaV 1.7 mRNA transcripts in nearly all retrogradely labelled colonic neurons, suggesting redundancy in function. By contrast, using comparative somatic behavioural models we identify that genetic deletion of NaV 1.7 (in NaV 1.8-expressing neurons) regulates noxious heat pain threshold and that this can be recapitulated by the selective NaV 1.7 antagonist PF-5198007. Our data demonstrate that NaV 1.7 (in NaV 1.8-expressing neurons) contributes to defined pain pathways in a modality-dependent manner, modulating somatic noxious heat pain, but is not required for visceral pain processing, and advocate that pharmacological block of NaV 1.7 alone in the viscera may be insufficient in targeting chronic visceral pain.

Effects of Acupuncture on Sleeping Time and Striatum 5-HT and DA Content in Rats with ;Stress Induced Gastric Mucosal Injury / 中国中医药信息杂志

Objective To observe the effects of acupuncture on the sleeping quality of male Wistar rats with stress induced gastric mucosal injury from the viewpoint of the brain-intestine axis. Methods Male Wistar rats were randomized into normal control, model, ST36-CV12, BL62-KI6, and combined groups, with 8 rats in each group. The model was established by using intragastric perfusion of ethanol in the rats. Acupoints of Zusanli (ST36) and Zhongwan (CV12) on both sides were used for the ST36-CV12 group. Acupoints of Shenmai (BL62) and Zhaohai (KI6) on both sides were used for the BL62-KI6 group. All four acupoints were used for the combined group. 0.22 mm × 13 mm stainless steel filiform needles were inserted 5-10 mm deep, and were left untouched for 20 minutes before withdrawal. The acupoints were stimulated each day for five days and the paw withdraw thermal latency (PWTL) was detected after the last stimulation. 2%pentobarbital sodium was then injected (40 mg/kg), and sleeping time of rats was detected. Gastric mucosa was observed through naked eyes. Gastric mucosal ulcer Index was determined by using the Guth method. 5-HT and DA contents were detected by using HPLC-ECD method. Results Compared with the normal control group, PWTL and sleeping time decreased (P<0.01), and UI, 5-HT, and DA content increased in model group (P<0.05, P<0.01). Compared with the model group, PTWL and sleeping time increased (P<0.05, P<0.01), and UI decreased in all treatment groups (P<0.01). 5-HT content in ST36-CV12 and combined groups decreased significantly, and DA content in ST36-CV12 group dropped (P<0.01). Compared with other treatment groups, PWTL and sleeping time increased significantly (P<0.01), and UI decreased obviously in combined group (P<0.01). Conclusion Stimulating acupoints of Zusanli, Zhongwan, Shenmai, and Zhaohai (KI6) may promote the recovery of gastric mucosal injury while at the same time increase sleeping time, with four acupoints used in combination having the best efficacy. The mechanism may be related to adjusting contents of 5-HT and DA in corpus striatum.

Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses.

Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive transient receptor potential ankyrin (TRPA)-1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42 °C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue.

Effects of different durations of warm-tube moxibustion by using near infrared spectroscopy / 全日本鍼灸学会雑誌

[Objective]Although warm-tube moxibustion is easy-to-use in acupuncture therapy, the timing of moxa removal varies among practitioners. In the present study, we used near infrared spectroscopy (NIRS) to compare effects of different durations of moxibustion stimulation on improvement in local circulation as measured by changes in blood oxygenation dynamics in muscle tissue.<BR>[Methods]Twelve healthy adults underwent warm-tube moxibustion with a single cone applied to the upper right shoulder region;measurements of tissue blood oxygenation dynamics (ΔOxy-Hb, ΔTotal-Hb) were obtained at intervals of 0.5 s. Control measurements were first taken for 15 min without intervention (Control);then, subjects received moxibustion 2 min after the start of measurement and had the moxa removed at the following time points: 30 s after patients experienced heat pain (Removal 30, moxibustion group); 45 s after heat pain (Removal 45, moxibustion group);or did not have the moxa removed (Continuous moxibustion group). These 4 different conditions were compared. Additionally, we determined the burning temperature of moxa and the skin temperature and intensity of heat pain sensation at the site of moxibustion.<BR>[Results]Compared with the Control, the Removal 30, Removal 45, and Continuous moxibustion groups had significant increases in ΔOxy-Hb, ΔTotal-Hb, and skin temperature, with no significant differences among the moxibustion groups. No significant difference in the intensity of heat pain sensation was observed among the moxibustion groups. All moxibustion groups began to show rapid increases in both ΔTotal-Hb and ΔOxy-Hb around the time when subjects began to feel heat pain, suggesting that the axon reflex evoked by noxious stimuli of heat pain increased blood volume and arterial blood flow.<BR>[Conclusion]Hemodynamic improvement in muscle tissue through the use of continuous warm-tube moxibustion for 30 s or longer after the occurrence of heat pain was confirmed.