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.

IonicRF™: a novel step in technology for radiofrequency ablation treatments

Radiofrequency ablation (RFA) has been utilized since the 1970s to treat various painful conditions. The technology has evolved from its initial use to treat lumbar facet mediated pain with monopolar lesioning to now treat a plethora of chronic pain conditions. This article reviews Abbott Corporation's (IL, USA) IonicRF™ generator. The IonicRF generator utilizes an intelligent power algorithm that improves efficiency and reduces procedure time. The generator also carries a wide range of RFA therapies such as monopolar, bipolar, pulsed or pulsed dose radiofrequency. Additionally, the IonicRF RFA generator is compatible with the Simplicity™ RF probe (Abbott) which allows for efficient and effective denervation of the sacroiliac joint.

Relief of neuropathic pain by cell-specific manipulation of nucleus accumbens dopamine D1- and D2-receptor-expressing neurons

Emerging evidence suggests that the mesolimbic dopaminergic network plays a role in the modulation of pain. As chronic pain conditions are associated with hypodopaminergic tone in the nucleus accumbens (NAc), we evaluated the effects of increasing signaling at dopamine D1/D2-expressing neurons in the NAc neurons in a model of neuropathic pain induced by partial ligation of sciatic nerve. Bilateral microinjection of either the selective D1-receptor (Gs-coupled) agonist Chloro-APB or the selective D2-receptor (Gi-coupled) agonist quinpirole into the NAc partially reversed nerve injury-induced thermal allodynia. Either optical stimulation of D1-receptor-expressing neurons or optical suppression of D2-receptor-expressing neurons in both the inner and outer substructures of the NAc also transiently, but significantly, restored nerve injury-induced allodynia. Under neuropathic pain-like condition, specific facilitation of terminals of D1-receptor-expressing NAc neurons projecting to the VTA revealed a feedforward-like antinociceptive circuit. Additionally, functional suppression of cholinergic interneurons that negatively and positively control the activity of D1- and D2-receptor-expressing neurons, respectively, also transiently elicited anti-allodynic effects in nerve injured animals. These findings suggest that comprehensive activation of D1-receptor-expressing neurons and integrated suppression of D2-receptor-expressing neurons in the NAc may lead to a significant relief of neuropathic pain.

Possibilities of colecalciferol therapy for tension type headache combined with hypovitaminosis D

Introduction. Modern studies indicate the therapeutic effect of vitamin D (VD) in chronic pain conditions, but there is no data on the use of VD in chronic tension type headache (CTTH) treatment.Objective: comparative evaluation of the effectiveness of various options for preventive treatment of CTTH: the use of colecalciferol, standard therapy of the disease and a combination of these methods.Materials and methods. 125 women with CTTH and hypovitaminosis D were treated in the study. The frequency, duration and intensity of headache (HF, HD and HI, respectively), HIT index, frequency of analgesics taking, pericranial muscle dysfunction were evaluated. The VD level was measured by the concentration of 25-hydroxyvitamin D [25(OH)D]. The patients received differentiated therapy for 16 weeks: group 1 – colecalciferol, group 2 – amitriptyline, group 3 – a combination of these medicines. Results. In group 1, HF, HD, HIT-index and the frequency of analgesics taking decreased, all p ≤ 0.001. In groups 2 and 3, the values of all CTTH-parameters decreased, all p < 0.05. HF, HIT-index and the frequency of analgesics taking in group 3 decreased more than in group 2, all p >< 0.017. In women who had VD deficiency before treatment, the decrease in HF from the initial one was 36% in group 1, 55% in group 2, and 74% in group 3. In patients who had VD deficiency before treatment, the effectiveness of therapy in group 3 was higher than in group 2: 74% vs. 55%, respectively, p >< 0.001.Conclusions. Treatment of hypovitaminosis D in women with CTTH is accompanied by a decrease in HF, the effect of headache on the quality of life of patients and the frequency of taking analgesics. In CTTH and VD deficiency normalization of 25(OH)D level contributes to higher efficiency of standard therapy.

Brain Imaging Biomarkers for Chronic Pain

The prevalence of chronic pain has reached epidemic levels. In addition to personal suffering chronic pain is associated with psychiatric and medical co-morbidities, notably substance misuse, and a huge a societal cost amounting to hundreds of billions of dollars annually in medical cost, lost wages, and productivity. Chronic pain does not have a cure or quantitative diagnostic or prognostic tools. In this manuscript we provide evidence that this situation is about to change. We first start by summarizing our current understanding of the role of the brain in the pathogenesis of chronic pain. We particularly focus on the concept of learning in the emergence of chronic pain, and the implication of the limbic brain circuitry and dopaminergic signaling, which underly emotional learning and decision making, in this process. Next, we summarize data from our labs and from other groups on the latest brain imaging findings in different chronic pain conditions focusing on results with significant potential for translation into clinical applications. The gaps in the study of chronic pain and brain imaging are highlighted in throughout the overview. Finally, we conclude by discussing the costs and benefits of using brain biomarkers of chronic pain and compare to other potential markers.

Ketamine for Non-Neuropathic Pain

Chronic pain is one of the leading causes of years lost to disability, as most of the time it is refractory to conventional treatment. Recent advances in understanding the pain mechanisms have favored the use of ketamine as a rescue agent in refractory chronic pain conditions, as it has potential modulating effect on both sensory-discriminative and affective motivational components of pain. Preclinical studies also suggested the antinociceptive effect of sub anesthetic dose of ketamine against central and peripheral neuropathic pain conditions and non-neuropathic pain conditions such as inflammatory and nociceptive pain states. Subanesthetic infusion of ketamine along with adjuvants such as midazolam and clonidine is found to reduce the psychomimetic and cardiovascular side effects of ketamine. Even though the consensus guidelines for intravenous use of ketamine for chronic pain advocate the use of ketamine only for complex regional pain syndrome, various other clinical studies suggested its role in other refractory painful conditions. Hence the present topic focuses specifically on the effect of ketamine on non-neuropathic pain conditions such as complex regional pain syndrome, fibromyalgia, headache, ischemic limb pain, etc. Many studies had shown that ketamine not only reduces the pain scores but also the analgesic medications, which further improves the well-being and quality of life.

Mirogabalin as a Novel Gabapentinoid for the Treatment of Chronic Pain Conditions: An Analysis of Current Evidence

: Neuropathic pain has presented a challenge for physicians to treat and often requires a multimodal approach with both pharmacologic and lifestyle interventions. Mirogabalin, a potent, selective ligand of the α2δ-1 and α2δ-2 subunits of voltage-gated calcium channels (VGCCs), provides analgesia by inhibiting neurotransmitter release at the presynaptic end of the neuron. Mirogabalin offers more sustained analgesia than its gabapentinoid counterparts in addition to a wider safety margin for adverse events. Recent clinical trials of mirogabalin have demonstrated both efficacy and tolerability of the drug for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia, leading to its approval in Japan. While still not yet FDA approved, mirogabalin is still in its infancy and offers potential into the treatment of neuropathic pain and its associated comorbidities.

Application of Theory in Chronic Pain Rehabilitation Research and Clinical Practice

Introduction: Chronic pain has multiple aetiological factors and complexity. Pain theory helps us to guide and organize our thinking to deal with this complexity. The objective of this paper is to critically review the most influential theory in pain science history (the gate control theory of pain) and focus on its implications in chronic pain rehabilitation to minimize disability. Methods: In this narrative review, all the published studies that focused upon pain theory were retrieved from Ovoid Medline (from 1946 till present), EMBAS, AMED and PsycINFO data bases. Results: Chronic pain is considered a disease or dysfunction of the nervous system. In chronic pain conditions, hypersensitivity is thought to develop from changes to the physiological top-down control (inhibitory) mechanism of pain modulation according to the pain theory. Pain hypersensitivity manifestation is considered as abnormal central inhibitory control at the gate controlling mechanism. On the other hand, pain hypersensitivity is a prognostic factor in pain rehabilitation. It is clinically important to detect and manage hypersensitivity responses and their mechanisms. Conclusion: Since somatosensory perception and integration are recognized as a contributor to the pain perception under the theory, then we can use the model to direct interventions aimed at pain relief. The pain theory should be leveraged to develop and refine measurement tools with clinical utility for detecting and monitoring hypersensitivity linked to chronic pain mechanisms.