Preventing Episodic Migraine With Caloric Vestibular Stimulation: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the safety and efficacy of a novel solid-state, caloric vestibular stimulation (CVS) device to provide adjuvant therapy for the prevention of episodic migraine in adult migraineurs. BACKGROUND: Migraine causes significant disability in ∼12% of the world population. No current migraine preventive treatment provides full clinical relief, and many exhibit high rates of discontinuation due to adverse events. Thus, new therapeutic options are needed. CVS may be an effective and safe adjuvant-therapy for the prevention of episodic migraine. METHODS: In a multicenter, parallel-arm, block-randomized, placebo-controlled clinical trial (clinicaltrials.gov: NCT01899040), subjects completed a 3-month treatment with the TNM™ device for CVS (refer to Fig. 2 for patient enrollment and allocation). The primary endpoint was the change in monthly migraine days from baseline to the third treatment month. Secondary endpoints were 50% responder rates, change in prescription analgesic usage and difference in total subjective headache-related pain scores. Device safety assessments included evaluation of any impact on mood, cognition, or balance. RESULTS: Per-protocol, active-arm subjects showed immediate and continued steady declines in migraine frequency over the treatment period. After 3 months of treatment, active-arm subjects exhibited significantly fewer migraine days (-3.9 ± 0.6 from a baseline burden of 7.7 ± 0.5 migraine days). These improvements were significantly greater than those observed in control subjects (-1.1 ± 0.6 from a baseline burden = 6.9 ± 0.7 migraine days) and represented a therapeutic gain of -2.8 migraine days, CI = -0.9 to -4.7, P = .012. Active arm subjects also reported greater reductions in acute medication usage and monthly pain scores compared to controls. No adverse effects on mood, cognition, or balance were reported. Subjects completed the trial with an average rate of 90% treatment adherence. No serious or unexpected adverse events were recorded. The rate of expected adverse events was similar across the active and the placebo groups, and evaluation confirmed that subject blinding remained intact. CONCLUSION: The TNM™ device for CVS appears to provide a clinically efficacious and highly tolerable adjuvant therapy for the prevention of episodic migraine.

Cool OtOprotective Ear Lumen (COOL) Therapy for Cisplatin-induced Hearing Loss.

HYPOTHESIS: Localized cooling of the external ear has a protective effect on the susceptibility to cisplatin-induced hearing loss. BACKGROUND: We previously demonstrated significant protection from cisplatin-induced hearing loss using cool water ear canal irrigation. However, the study was limited to a single bolus injection of cisplatin and an acute time period. Here, we examined the application of localized cooling of the ear canal with repeated doses of cisplatin, over an expanded period of time, and using two methods of cooling. METHODS: Twenty-four guinea pigs (12 male and 12 female) underwent auditory physiological testing (auditory brainstem response and distortion product otoacoustic emissions at 8-32 kHz) and pre/postadministration of cisplatin. Cisplatin (4 mg/kg i.p.) was administered in 3 weekly single injections for a total of 12 mg/kg. While anesthetized, the left ears of the guinea pigs were exposed to either cool water (22°C; ICS Water Caloric Irrigator), a cool ear bar (15°C, cooled by a Peltier device; TNM, Scion NeuroStim), or left uncooled as a sham control. The animals were tested 3 days post each dosage and 1 month post the final dose. At the end of the experiment the animals were euthanized for histological evaluation. RESULTS: We found that hearing loss was significantly reduced, and hair cell survival greatly improved, in animals that received cooling treatments compared to cisplatin-only control animals. No significant difference was observed between the two methods of cooling. CONCLUSION: Localized cooling of the ear canal during administration of cisplatin mitigated loss of auditory function and loss of hair cells.

Sensory Neuromodulation.

We describe a model of neurological disease based on dysfunctional brain oscillators. This is not a new model, but it is not one that is widely appreciated by clinicians. The value of this model lies in the predictions it makes and the utility it provides in translational applications, in particular for neuromodulation devices. Specifically, we provide a perspective on devices that provide input to sensory receptors and thus stimulate endogenous sensory networks. Current forms of clinically applied neuromodulation, including devices such as (implanted) deep brain stimulators (DBS) and various, noninvasive methods such as transcranial magnetic stimulation (TMS) and transcranial current methods (tACS, tDCS), have been studied extensively. The potential strength of neuromodulation of a sensory organ is access to the same pathways that natural environmental stimuli use and, importantly, the modulatory signal will be transformed as it travels through the brain, allowing the modulation input to be consistent with regional neuronal dynamics. We present specific examples of devices that rely on sensory neuromodulation and evaluate the translational potential of these approaches. We argue that sensory neuromodulation is well suited to, ideally, repair dysfunctional brain oscillators, thus providing a broad therapeutic approach for neurological diseases.

Non-Invasive Neuromodulation Using Time-Varying Caloric Vestibular Stimulation.

Caloric vestibular stimulation (CVS) to elicit the vestibulo-ocular reflex has long been used in clinical settings to aid in the diagnosis of balance disorders and to confirm the absence of brainstem function. While a number of studies have hinted at the potential therapeutic applications of CVS, the limitations of existing devices have frustrated that potential. Current CVS irrigators use water or air during short-duration applications; however, this approach is not tenable for longer duration therapeutic protocols or home use. Here, we describe a solid-state CVS device we developed in order to address these limitations. This device delivers tightly controlled time-varying thermal waveforms, which can be programmed through an external control unit. It contains several safety features, which limit patients to the prescribed waveform and prevent the potential for temperature extremes. In this paper, we provide evidence that CVS treatment with time-varying, but not constant temperature waveforms, elicits changes in cerebral blood flow physiology consistent with the neuromodulation of brainstem centers, and we present results from a small pilot study, which demonstrate that the CVS can safely and feasibly be used longitudinally in the home setting to treat episodic migraine. Together, these results indicate that this solid-state CVS device may be a viable tool for non-invasive neuromodulation.

Self-compassion in patients with persistent musculoskeletal pain: relationship of self-compassion to adjustment to persistent pain.

CONTEXT: Self-compassion entails qualities such as kindness and understanding toward oneself in difficult circumstances and may influence adjustment to persistent pain. Self-compassion may be a particularly influential factor in pain adjustment for obese individuals who suffer from persistent pain, as they often experience heightened levels of pain and lower levels of psychological functioning. OBJECTIVES: The purpose of the present study was to examine the relationship of self-compassion to pain, psychological functioning, pain coping, and disability among patients who have persistent musculoskeletal pain and who are obese. METHODS: Eighty-eight obese patients with persistent pain completed a paper-and-pencil self-report assessment measure before or after their appointment with their anesthesiologist. RESULTS: Hierarchical linear regression analyses demonstrated that even after controlling for important demographic variables, self-compassion was a significant predictor of negative affect (ß=-0.48, P<0.001), positive affect (ß=0.29, P=0.01), pain catastrophizing (ß=-0.32, P=0.003), and pain disability (ß=-0.24, P<0.05). CONCLUSION: The results of this study indicate that self-compassion may be important in explaining the variability in pain adjustment among patients who have persistent musculoskeletal pain and are obese.

Pain acceptance, hope, and optimism: relationships to pain and adjustment in patients with chronic musculoskeletal pain.

UNLABELLED: There is growing interest in the role that positive aspects of psychological adjustment, such as pain acceptance, hope, and optimism, may play in explaining adjustment in persons suffering from persistent pain. This study conducted in obese patients with persistent musculoskeletal pain (N = 89) examined the degree to which pain acceptance and hope explained pain intensity, pain unpleasantness, psychological distress, and pain-related disability, after controlling for the effects of optimism. In correlational analyses, pain acceptance and optimism were associated with psychological distress and pain disability with hope being related to only psychological distress. Pain acceptance, optimism, and hope were not significantly associated with pain. Hierarchical linear regression (HLR) analyses found that pain acceptance remained a significant predictor of psychological distress and pain disability after controlling for optimism, demographic, and medical variables. HLR analyses found that hope was not a significant predictor of psychological distress after controlling for optimism, pain acceptance, and demographic and medical variables. The results of this study are important because they indicate that pain acceptance, hope, and optimism are all related to pain adjustment. They also highlight the importance of controlling for optimism when examining the effects of pain acceptance and hope on pain adjustment. PERSPECTIVE: In a sample of obese patients with persistent musculoskeletal pain, pain acceptance was a significant predictor of psychological distress and pain disability even after controlling for optimism, demographic, and medical variables. These results add to the growing literature on the importance of pain acceptance in understanding adjustment to persistent pain.