Priming of central- and peripheral mechanisms with heat and cutaneous capsaicin facilitates secondary hyperalgesia to high frequency electrical stimulation

Heat/capsaicin sensitization and electrical high frequency stimulation (HFS) are well known model of secondary hyperalgesia, a phenomenon related to chronic pain conditions. This study investigated whether priming with heat/capsaicin would facilitate hyperalgesia to HFS in healthy subjects. Heat/capsaicin priming consisted of a 45 °C heat stimulation for 5 min followed by a topical capsaicin patch (4x4 cm) for 30 minutes on the volar forearm of 20 subjects. HFS (100 Hz, 5 times 1s, minimum 1.5 mA) was subsequently delivered through a transcutaneous pin electrode approximately 1.5 cm proximal to the heat/capsaicin application. Two sessions were applied in a crossover design; traditional HFS (HFS) and heat/capsaicin sensitization followed by HFS (HFS+HEAT/CAPS). Heat pain threshold (HPT), mechanical pain sensitivity (MPS) and superficial blood perfusion were assessed at baseline, after capsaicin removal, and up to 40 min after HFS. MPS was assessed with pinprick stimulation (128 mN and 256 mN) in the area adjacent to both HFS and heat/capsaicin, distal but adjacent to heat/capsaicin and in a distal control area. HPT was assessed in the area of heat/capsaicin. Higher sensitivity to 128 mN pinprick stimulation (difference from baseline and control area) was observed in the HFS+HEAT/CAPS session than in the HFS session 20 and 30 minutes after HFS. Furthermore, sensitivity was increased after HFS+HEAT/CAPS compared to after heat/capsaicin in the area adjacent to both paradigms, but not in the area distal to heat/capsaicin. Results indicate that heat/capsaicin causes priming of the central- and peripheral nervous system, which facilitates secondary mechanical hyperalgesia to HFS.

A Systematic Review on Cannabis Hyperemesis Syndrome and its Management Options

Introduction: Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V, associated with chronic cannabis use among adults and older patients have been reported named cannabis hyperemesis syndrome (CHS). CHS is a condition that leads to repeated and severe N/V in long-term users of cannabinoids. Objective: To outline current treatments for the management of CHS. Methods: A systematic review was conducted using PubMed, Ovid MEDLINE, Cochrane Central, EMBASE and Google Scholar. Databases were used to search for articles on CHS published from January 2009 to June 2021, yielding 225 results of which 17 were deemed relevant and underwent review by two separate reviewers. Results: The duration of cannabis administration ranged between six months to 11 years may precipitate symptoms of CHS. The Rome IV diagnostic criteria of CHS requires cannabinoid use and persistence if N/V symptoms for at least the past six months. Cannabis cessation is noted to be the most successful management, but other treatments also demonstrated symptom relief and included hot water hydrotherapy, topical capsaicin cream, haloperidol, droperidol, benzodiazepines, propranolol and aprepitant administration. Conclusion: Overall future research on CHS is needed which enhance knowledge translation, education and creates awareness of the medical community about the side effects of cannabinoids and propose the best treatment options.

Renal Deafferentation Prevents Progression of Hypertension and Changes to Sympathetic Reflexes in a Rabbit Model of Chronic Kidney Disease

There is increasing evidence that renal denervation is effective in alleviating hypertension associated with elevation of renal sympathetic nerve activity (RSNA) in chronic kidney disease (CKD), but whether this is due to reduction in renal afferent signaling is unclear. We determined the cardiovascular and sympathetic effects of total renal denervation or afferent renal denervation (topical capsaicin) on CKD induced by glomerular layer lesioning of the left kidney and right nephrectomy in conscious rabbits. CKD increased blood pressure by 18±2 mmHg and plasma creatinine by 40% over 2 to 4 weeks (both P <0.001), while RSNA (43%) and total norepinephrine spillover (28%) were elevated in CKD compared with sham (both P =0.04). After total or afferent renal denervation blood pressure, RSNA and norepinephrine spillover were similar or lower than non-CKD (sham) rabbits. While plasma creatinine in CKD rabbits was not affected by total renal denervation, deafferented rabbits had lower levels ( P =0.017). The greater hypotensive response to pentolinium in CKD was also normalized after total or afferent denervation. Heart rate and RSNA baroreflex gain were similar in all groups. The RSNA response to airjet stress was greater in CKD compared with sham but not after total or afferent renal denervation. By contrast, the sympathetic response to hypoxia was similar in sham and CKD intact or deafferented groups but elevated in total denervated CKD animals. We conclude that the elevated sympathetic activity and blood pressure in this model of CKD is predominantly driven by renal afferents.

Topical Capsaicin for the Treatment of Sensory Neuropathic Cough

Objective To evaluate a novel treatment for sensory neuropathic cough (SNC): topical capsaicin. Study Design Retrospective review. Setting Tertiary care laryngology clinic. Methods A retrospective review was performed on 201 consecutive patients treated for SNC with capsaicin 0.02% to 0.04% applied topically to the upper aerodigestive tract, typically after failure of standard medications. Patients were asked to use the spray 4 times daily for 2 weeks prior to assessment of benefit. Items assessed included the percentage reduction of coughing, type of benefit noted, and side effects. Results Of the 201 patients who used the spray, 36.3% noted no benefit, whereas 63.7% (n = 128) had benefit in terms of cough reduction: 30.8% (n = 62) reported ≥75% reduction; 17.4% (n = 35), 50%-74% reduction; 7.0% (n = 14), 25%-49% reduction; and 8.5% (n = 17), 1%-24% reduction. Of all patients, 78.3% reported no side effects or complications. Of the remaining 21.7%, 1 patient noted a nosebleed after a single administration, and 1 patient noted transient wheezing after administration. The others reported unpleasant local effects, including throat/ear discomfort, voice change, sneezing, reflexive vomiting, and headache. Conclusion In our group of 201 patients with SNC, most of which had failed to respond to standard treatments, 63.7% had some response to capsaicin spray, with 30.8% reporting ≥75% reduction. Minimal side effects of treatment were reported. Thus, we suggest that this therapy can be another treatment option for patients with SNC.

A Review on Various Topics on the Thermal Grill Illusion

The thermal grill illusion (TGI) is a paradoxical perception of burning heat and pain resulting from the simultaneous application of interlaced warm and cold stimuli to the skin. The TGI is considered a type of chronic centralized pain and has been used to apply nociceptive stimuli without inflicting harm to human participants in the study of pain mechanisms. In addition, the TGI is an interesting phenomenon for researchers, and various topics related to the TGI have been investigated in several studies, which we will review here. According to previous studies, the TGI is generated by supraspinal interactions. To evoke the TGI, cold and warm cutaneous stimuli should be applied within the same dermatome or across dermatomes corresponding to adjacent spinal segments, and a significant difference between cold and warm temperatures is necessary. In addition, due the presence of chronic pain, genetic factors, and sexual differences, the intensity of the TGI can differ. In addition, cold noxious stimulation, topical capsaicin, analgesics, self-touch, and the presence of psychological diseases can decrease the intensity of the TGI. Because the TGI corresponds to chronic centralized pain, we believe that the findings of previous studies can be applied to future studies to identify chronic pain mechanisms and clinical practice for pain management.

Chiropractic Spinal Manipulation Prevents Secondary Hyperalgesia Induced by Topical Capsaicin in Healthy Individuals

Background and Aims: Spinal manipulation (SM) is currently recommended for the management of back pain. Experimental studies indicate that the hypoalgesic mechanisms of SM may rely on inhibition of segmental processes related to temporal summation of pain and, possibly, on central sensitization, although this remains unclear. The aim of this study was to determine whether experimental back pain, secondary hyperalgesia, and pain-related brain activity induced by capsaicin are decreased by segmental SM.Methods: Seventy-three healthy volunteers were randomly allocated to one of four experimental groups: SM at T5 vertebral level (segmental), SM at T9 vertebral level (heterosegmental), placebo intervention at T5 vertebral level, or no intervention. Topical capsaicin was applied to the area of T5 vertebra for 40 min. After 20 min, the interventions were administered. Pressure pain thresholds (PPTs) were assessed outside the area of capsaicin application at 0 and 40 min to examine secondary hyperalgesia. Capsaicin pain intensity and unpleasantness were reported every 4 min. Frontal high-gamma oscillations were also measured with electroencephalography.Results: Pain ratings and brain activity were not significantly different between groups over time (p &gt; 0.5). However, PPTs were significantly decreased in the placebo and control groups (p &lt; 0.01), indicative of secondary hyperalgesia, while no hyperalgesia was observed for groups receiving SM (p = 1.0). This effect was independent of expectations and greater than placebo for segmental (p &lt; 0.01) but not heterosegmental SM (p = 1.0).Conclusions: These results indicate that segmental SM can prevent secondary hyperalgesia, independently of expectations. This has implications for the management of back pain, particularly when central sensitization is involved.