Progressive Response to Repeat Application of Capsaicin 179 mg (8% w/w) Cutaneous Patch in Peripheral Neuropathic Pain: Comprehensive New Analysis and Clinical Implications.

OBJECTIVE: To investigate the efficacy of repeated application of capsaicin 179 mg cutaneous patch in nonresponders to the first application. DESIGN: Post hoc, as-treated analysis of two prospective trials (STRIDE and PACE) with 52-week follow-up. BLINDING: Open-label. SETTING: Multicenter clinical trial. SUBJECTS: STRIDE: nondiabetic neuropathic pain; PACE: painful diabetic peripheral neuropathy. METHODS: Patients were divided according to number of applications needed before attainment of a ≥30% reduction in average pain intensity (question 5 of the Brief Pain Inventory [BPI-Q5]). We assessed the change from baseline in average pain intensity (BPI-Q5), mean "interference with sleep" score, Patient Global Impression of Change, quality of life (QOL) via the EuroQol 5-dimension, and Self-Assessment of Treatment. RESULTS: In STRIDE and PACE, respectively, n = 306 and n = 313 received the capsaicin patch; n = 60 and n = 96 had a response after the first application, n = 33 and n = 68 after the second, and n = 11 and n = 43 after the third. Among patients without a ≥30% reduction in pain intensity at 3 months, in STRIDE and PACE, respectively, 23.3% and 28.1% achieved a ≥30% reduction at 6 months, increasing to 33.9% and 45.7% at 12 months. Similar results were obtained when a decrease of ≥50% was used as the responder definition. Progressive improvements in pain intensity in slower responders reached levels similar to those in early responders at month 12 and were accompanied by improvements in sleep, QOL, and patient satisfaction. CONCLUSIONS: Although some patients with peripheral neuropathic pain experience rapid improvements with a single treatment of capsaicin 179 mg patch, some may require two or three treatments before an initial response is observed. Similar benefits for pain, sleep, and QOL can be achieved in early and late responders.

The Acute Effect of Skin Preheating on Capsaicin-Induced Central Sensitization in Humans.

INTRODUCTION: Topical capsaicin is commonly employed to experimentally induce central sensitization (CS) in humans. While previous studies have investigated the effect of skin preheating on the sensitizing effect of capsaicin, no studies have compared the synergistic effect of skin preheating on the magnitude of sensitization via topical capsaicin within the first 30 minutes of application. We tested the hypothesis that skin preheating potentiates the sensitizing effect of topical capsaicin by evoking a larger region of secondary hyperalgesia vs. topical capsaicin alone. METHODS: Twenty young, healthy subjects each received topical capsaicin (Zostrix HP 0.075%) only (CAP), topical capsaicin with preheating (CAP + HEAT), and topical nonsensitizing placebo cream (CON) in a crossover design. Capsaicin and placebo creams were applied to a 50 cm2 area of the dorsal forearm. The CAP + HEAT session also included a 10-minute preheating session. Regions of secondary hyperalgesia were assessed using mechanical brush allodynia testing, and skin temperature was assessed via infrared thermography. Outcomes were normalized to baseline and compared at 10, 20, and 30 minutes after cream application. RESULTS: The CAP + HEAT session led to a significantly larger area of secondary hyperalgesia compared to the CAP session as measured by brush allodynia (CON: 0 ± 0 cm; CAP: 2.08 ± 0.45 cm; CAP + HEAT: 3.70 ± 0.46 cm; P < 0.05) and skin temperature (CON: -2.92% ± 0.03%; CAP: -0.63% ± 0.09%; CAP + HEAT: 2.50% ± 0.11%; ( of baseline) P < 0.05). CONCLUSION: Preheating amplifies the sensitizing effect of topical capsaicin within 30 minutes of application. The heat-capsaicin technique may be employed to assess differing magnitudes of CS induction and enables future studies investigating the development and progression of CS in humans.

Does Topical Capsaicin Affect the Central Nervous System in Neuropathic Pain? A Narrative Review.

Research has been conducted investigating the neuronal pathways responsible for the generation of chronic neuropathic pain, including the components of it in conditions such as chronic post-surgical pain, phantom limb pain, and cluster headaches. Forming part of the management of such conditions, capsaicin as a molecule has proven effective. This review has investigated the central nervous system modifications exhibited in such conditions and the pharmacological mechanisms of capsaicin relevant to this. The current paradigm for explaining topical capsaicin-induced analgesia is that TRPV1-mediated calcium ion influx induces calpain, in turn causing axonal ablation and functional defunctionalisation in the PNS (Peripheral Nervous System). Demonstrated through the analysis of existing data, this review demonstrates the changes seen in the CNS (Central Nervous System) in chronic neuropathic pain, as well as some of the evidence for capsaicin modulation on the CNS. Further supporting this, the specific molecular mechanisms of capsaicin-induced analgesia will also be explored, including the action of TRPV1, as well as discussing the further need for clinical research into this area of uncertainty due to the limited specific data with suitable parameters. Further research this review identified as potentially useful in this field included fMRI (functional Magnetic Resonance Imaging) studies, though more specific observational studies of patients who have already been administered capsaicin as a current treatment may prove helpful in studying the modification of the CNS in the long term.

Capsaicin, its clinical significance in patients with painful diabetic neuropathy.

Diabetic neuropathy is a risk factor for developing complications such as autonomic cardiovascular disease, osteoarthropathy, foot ulcers, and infections, which may be the direct cause of death. Even worse, patients plagued by this condition display painful neuropathic symptoms that are usually severe and frequently lead to depression, anxiety, and sleep disarrays, eventually leading to a poor quality of life. There is a general interest in evaluating the therapeutic properties of topical capsaicin cream as an effective agent for pain relief in these patients. As such, the current review makes use of major search engines like PubMed and Google Scholar, to bring an updated analysis of clinical studies reporting on the therapeutic effects of capsaicin in patients with painful diabetic neuropathy. In fact, most of the summarized literature indicates that topical capsaicin (0.075 %) cream, when applied to the painful areas for approximately 8 weeks, can reduce pain, which may lead to clinical improvements in walking, working, and sleeping in patients with painful diabetic neuropathy. The current review also discusses essential information on capsaicin, including its source, bioavailability profile, as well as treatment doses and duration, to highlight its therapeutic potential.

Primary Erythromelalgia Treated With 10% Capsaicin Cream: A Case Report and a 10-Year Follow-Up.

In this case report, we describe the difficulty in finding a suitable treatment for a nine-year-old girl with erythromelalgia. Initially, she could only find pain relief through immersion of her hands and feet in buckets of cool water. Her pain did not respond to outpatient treatments, and she was ultimately admitted to the hospital for pain management. Many different medications and modalities were tried over the course of several weeks in the hospital. Finally, she received the most benefit from 10% compounded capsaicin cream administered under general anesthesia with regional analgesia for post-application pain. Over the course of several years, exacerbations of her pain were treated with additional applications of 10% capsaicin cream, with each application providing relief for an increased duration. Her severe pain flares eventually went into remission after several years. Today, after more than a decade following her initial presentation, she is a successful college student and is taking no medications for her erythromelalgia.

Capsaicin patch for persistent postoperative pain after thoracoscopic surgery, report of two cases.

Effective postoperative pain control after thoracic surgery is a significant clinical issue because it reduces pulmonary complications and accelerates the pace of recovery. Persistent postoperative pain syndrome is a recognized and frequent complication after thoracoscopic surgery. The capsaicin 8% patch contains a high concentration of synthetic capsaicin approved for treatment of peripheral neuropathic pain in adults. Little clinical data exist on the use of capsaicin patch in thoracic persistent postoperative pain syndrome. This report included two patients who were evaluated after receiving capsaicin for thoracic surgery. Satisfactory pain relief was achieved in both cases without side effects.

Low-concentration topical capsaicin for chronic neuropathic pain in adults.

To assess the efficacy and tolerability of topically applied low-concentration (less than 1%) capsaicin for treating chronic neuropathic pain in adults.

Postherpetic neuralgia: New hopes in prevention with adult vaccination and in treatment with a concentrated capsaicin patch.

Background and purpose Postherpetic neuralgia (PHN) is a complication of acute herpes zoster (HZ). The evidence base for management of PHN has increased by recent publications. Therefore, we reviewed incidence of HZ, prevalence, risk factors, and mechanism of PHN pain, prevention and treatment of PHN with special interest in studies on adult vaccination and topical application of lidocaine and concentrated capsaicin patch. Methods We searched databases with an English language restriction: MEDLINE 1944-2011, EMBASE 1988-2011, PubMed, and the Cochrane Controlled Trial Register and Cochrane Library (2011). From retrieved publications, we selected studies focusing on our main goals, prevention and treatment of PHN in particular. The review was therefore systematic, but with a pragmatic approach to which studies to select for closer review. Results From the large number of abstracts retrieved we selected 65 papers for closer review and as evidence base for our conclusions and recommendations for prevention and treatment of HZ and PHN. The incidence of HZ and risks of having PHN after HZ increases markedly with age above 60-70. Severity of symptoms and their impact on quality of life is a major health problem of persons above 70 years of age. Adult vaccination with the reinforced varicella virus vaccine reduces the incidence of HZ and PHN by about 50%. This is an important health and quality of life gain for the elderly. Antiviral drugs given early in an episode of HZ reduce pain and duration of HZ and decrease the risk of PHN. Pharmacological management of PHN are with nortriptyline (or amitriptyline in the younger patients), and or a gabapentinoid as first line drugs. Early treatment also is with topical lidocaine for immediate but short-lasting relief of burning hyperalgesia, and topical capsaicin relieving hypersensitivity for up to 12 weeks. A number of second and third line drugs have less evidence-base for effect, and often more adverse effects than the first line drugs: serotonin and noradrenaline uptake inhibitors (venlafaxin, duloxetin), antiepileptics (valproate), and opioid analgesics. Opioids are indicated for bridging in patients with severe PHN-symptoms while waiting for the more specific first line drugs to take effect. In these elderly patients, systemic pharmacological treatments are always a difficult balance between effects and adverse effects. It is important with close supervision of the patients, especially during start-up of systemically administered drugs, in order to prevent tragic complications from falls in sedated, dizzy, and confused elderly patients. Topical treatment with lidocaine and capsaicin patches does not have these problems. Conclusions Prevention of this significant health problem of the increasing elderly population is now possible through adult vaccination against varicella zoster virus (VZV) reactivation, as well as vigorous and early antiviral treatment during acute HZ. The evidence -base supports the oral use of tricyclic antidepressants, gabapentinoids, and opioids for bridging till the first line drugs take effect. Topical therapy with lidocaine and capsaicin patches is effective and well supported by evidence. A number of second and third line drugs and treatments are available, but have less evidence-base. All drug treatments, except topical lidocaine and capsaicin, have adverse effects that are often problematic and can be dangerous in the elderly patients. Close supervision of the patients is mandatory. Implications Recent advances in prevention and management of this serious health problem should be better known and implicated: Adult vaccination for prevention of varicella zoster virus reactivation, antiviral drugs and combinations of drugs can reduce the suffering from acute HZ and chronic PHN. Topical lidocaine and capsaicin are now evidence-based therapies that reduce suffering from hypersensitivity and hyperalgesia in patients with PHN. When properly applied, they have few complications.