Topical Application Of Capsaicin Research Articles

Quantitative sensory testing response patterns to capsaicin- and ultraviolet-B-induced local skin hypersensitization in healthy subjects: a machine-learned analysis.

The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain). This study provided a 246 × 10-sized data matrix (82 subjects assessed at baseline, following UV-B application, and following capsaicin application) with respect to 10 QST parameters, which we analyzed using machine-learning techniques. We observed statistically significant effects of the hypersensitization treatments in 9 different QST parameters. Supervised machine-learned analysis implemented as random forests followed by ABC analysis pointed to heat pain thresholds as the most relevantly affected QST parameter. However, decision tree analysis indicated that UV-B additionally modulated sensitivity to cold. Unsupervised machine-learning techniques, implemented as emergent self-organizing maps, hinted at subgroups responding to topical application of capsaicin. The distinction among subgroups was based on sensitivity to pressure pain, which could be attributed to sex differences, with women being more sensitive than men. Thus, while UV-B and capsaicin share a major component of heat pain sensitization, they differ in their effects on QST parameter patterns in healthy subjects, suggesting a lack of redundancy between these models.

Pharmacological cardiac sympathetic afferent denervation in pacing‐induced heart failure

Chronic sympathoexcitation is a hallmark of congestive heart failure. Enhanced input from the cardiac sympathetic afferent reflex (CSAR) appears to be a major contributor to augmented central sympathetic outflow in heart failure (HF) in rats (Myocardial ischemia model. Wang et al., Hypertension, 2014) and dogs (Rapid ventricular pacing model. Wang and Zucker, Am. J. Physiol., 1996). Transient receptor potential vanilloid 1 (TRPV1) expressing cardiac afferent fibers are responsible for CSAR activation, since systemic (Zahner et al., J. Physiol., 2003) and epicardial (Wang et al., Hypertension, 2014) administration of resiniferatoxin (RTX), an ultra‐potent analog of capsaicin that degenerates TRPV1‐expressing neurons, can almost completely abolish CSAR activation in rats. We tested whether epicardial application of RTX degenerates cardiac sympathetic TRPV1‐expressing neurons therefore reducing CSAR reactivity, in canines with pacing‐induced HF. In control studies, stimulation of left ventricular afferents containing TRPV1 via topical application of capsaicin (2 mg/ml) caused a pressor response and tachycardia (Δ=+15 mmHg, +44bpm). These responses were abolished by acute topical application of RTX (50 μg/mL). Experiments were repeated 9 weeks following RTX treatment and the subsequent induction of HF via rapid ventricular pacing. RTX pretreatment abolished the responses to capsaicin, whereas CSAR was preserved in HF if no RTX pretreatment was performed. TRPV1 expressing neuronal degeneration was evaluated through immunofluorescence histology (IFH) in left ventricle tissue samples, with triple labeling for DAPI (nuclei marker), PGP9.5 (nerve terminal marker,) and TRPV1 receptors. RTX treated tissue samples showed considerably lower TRPV1 positive staining when compared to non‐treated samples. The present study validates RTX as a potential therapeutic method to block excessive CSAR activation in pacing‐induced heart failure dogs, therefore expanding pharmacotherapy options for heart failureSupport or Funding InformationNIH HL55473 and HL126706

Somatosensory Profile Changes Evoked by Topical Application of Capsaicin to the Tongue in Healthy Individuals.

To assess the effect of topical application of capsaicin to the tongue as a surrogate model of burning mouth syndrome (BMS) on somatosensory sensitivity by using a standardized battery of quantitative sensory testing (QST) in healthy volunteers. This study comprised two experimental sessions (experimental [capsaicin] and control [Vaseline]) with QST in 16 healthy women. The examiner applied capsaicin or Vaseline to the tongue tip for 5 minutes. Each participant kept their tongue tip in contact with the capsaicin/Vaseline at the bottom of a disposable cup for 5 minutes, during which time the participant rated the perceived intensity of the tongue pain every 30 seconds on an electronic 0 to 10 visual analog scale (VAS). QST was performed on the tongue tip before and immediately after application in each session. The QST data were analyzed by two-way analysis of variance (ANOVA). Mean ± standard error of the mean (SEM) of VAS pain scores during the capsaicin and control sessions were 8.2 ± 0.5 and 1.9 ± 0.2, respectively. The peak of the perceived pain in the capsaicin session was significantly higher than in the control session (P < .001). In the capsaicin session, the postapplication heat pain threshold (HPT) was significantly higher than the preapplication HPT, and the postapplication cold detection threshold (CDT) and mechanical pain threshold (MPT) were significantly lower than before application (P < .001). The average z scores showed a significant somatosensory loss regarding CDT. In the control session, there were no differences between preapplication and postapplication values. Topical application of capsaicin to the tongue tip changed somatosensory sensitivity in healthy participants.

The Effectiveness and Safety of Topical Capsaicin in Postherpetic Neuralgia: A Systematic Review and Meta-analysis.

In particular, neuropathic pain is a major form of chronic pain. This type of pain results from dysfunction or lesions in the central and peripheral nervous system. Capsaicin has been traditionally utilized as a medicine to remedy pain. However, the effectiveness and safety of this practice is still elusive. Therefore, this systematic review aimed to investigate the effect of topical capsaicin as a pain-relieving agent that is frequently used in pain management. In brief, all the double-blinded, randomized placebo- or vehicle-controlled trials that were published in English addressing postherpetic neuralgia were included. Meta-analysis was performed using Revman® version 5.3. Upon application of the inclusion and exclusion criteria, only six trials fulfilled all the criteria and were included in the review for qualitative analysis. The difference in mean percentage change in numeric pain rating scale score ranges from -31 to -4.3. This demonstrated high efficacy of topical capsaicin application and implies that capsaicin could result in pain reduction. Furthermore, meta-analysis was performed on five of the included studies. All the results of studies are in favor of the treatment using capsaicin. The incidence of side effects from using topical capsaicin is consistently higher in all included studies, but the significance of safety data cannot be quantified due to a lack of p-values in the original studies. Nevertheless, topical capsaicin is a promising treatment option for specific patient groups or certain neuropathic pain conditions such as postherpetic neuralgia.

13. Which is the best evoked potential technique for assessing the nociceptive system? Preliminary results of a neurophysiological study in healthy humans

Laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs) are widely agreed method for investigating the nociceptive system. Concentric electrodes (CE) have also recently been introduced to measure pain-related evoked potentials (PREPs) and, thereby, to assess the nociceptive system in patients. Although some authors have reported that low intensity CE stimulation, evoking pinprick sensation, selectively activates nociceptive fibres, the CE reliability in the assessment of nociceptive system is still unclear. In this study we aimed to verify whether low and high intensity CE stimulations selectively activates nociceptive fibres. To do so we recorded LEPs, CHEPs and PREPs before and after capsaicin-induced skin denervation. To date, we have enrolled 6 healthy subjects. All subjects underwent a baseline recording of LEPs, CHEPs and PREPs after stimulation of the right forearm. For PREP recording we used both low intensity stimulation, evoking a distinct pinprick sensation and high intensity stimulation, evoking an electrical painless sensation. After the baseline evoked potential recordings, we applied an 8% capsaicin plaster on the right forearm. After one-two weeks, we recorded LEPs, CHEPs and PREPs after stimulation of the capsaicin-induced denervated forearm skin. In a small skin area spared by evoked potential stimulations we have also collected a skin biopsy for assessing the skin denervation. While LEPs and CHEPs were suppressed after topical application of capsaicin, low and high intensity PREPs did not differ before and after capsaicin-induced skin denervation. The skin biopsy documented the skin denervation induced by the capsaicin plaster. Our data indicate that both low and high intensity CE stimulation elicit PREPs after skin denervation, thus suggesting that the CE stimulation probably coactivates non-nociceptive fibres.

Perceptual distortion of the tongue by lingual nerve block and topical application of capsaicin in healthy women.

The aim of this study was to examine reports of perceptual distortion evoked by transient deafferentation and burning pain as models of aspects of burning mouth syndrome (BMS). Sixteen healthy women took part in three experimental sessions that included exposure to lingual nerve block, capsaicin, and control substance. In each session, reported perceptual distortion and mechanical detection threshold (MDT) were assessed at four areas (the tongue, lower front teeth, lower lip, and right thumb) before and at 5, 15, 30min and 1 and 3h after the injection or application. A numerical rating scale (NRS) and a template matching procedure were used to quantify the perceptual distortions. There was a significantly higher MDT on the tongue during the lingual nerve block session at 5min up until 1h, with the perceived tongue size significantly increased at 5, 15, and 30min and at 1h compared to baseline (P<0.05). Although the perceived size determined by the NRS scores during the capsaicin session was significantly larger for the lower lip at 5min compared to baseline (P<0.001), there were no significant effects on the MDT or the perceived sizes for the tongue, lower front teeth, or right thumb at any of the time points. Perceptual distortions of the tongue may be influenced by non-nociceptive somatosensory changes rather than nociceptive activity. The perceptual distortion of the tongue was investigated with models of aspects of BMS and may have implications for future studies in clinical populations.

Invitro activation of the neuro-transduction mechanism in sensitive organotypic human skin model.

Recent advances in tissue engineering have encouraged researchers to endeavor the production of fully functional three-dimensional (3D) thick human tissues invitro. Here, we report the fabrication of a fully innervated human skin tissue invitro that recapitulates and replicates skin sensory function. Previous attempts to innervate invitro 3D skin models did not demonstrate an effective functionality of the nerve network. In our approach, we initially engineer functional human skin tissue based on fibroblast-generated dermis and differentiated epidermis; then, we promote rat dorsal root ganglion (DRG) neurons axon ingrowth in the de-novo developed tissue. Neurofilaments network infiltrates the entire native dermis extracellular matrix (ECM), as demonstrated by immunofluorescence and second harmonic generation (SHG) imaging. To prove sensing functionality of the tissue, we use topical applications of capsaicin, an agonist of transient receptor protein-vanilloid 1 (TRPV1) channel, and quantify calcium currents resulting from variations of Ca++ concentration in DRG neurons innervating our model. Calcium currents generation demonstrates functional cross-talking between dermis and epidermis compartments. Moreover, through a computational fluid dynamic (CFD) analysis, we set fluid dynamic conditions for a non-planar skin equivalent growth, as proof of potential application in creating skin grafts tailored on-demand for invivo wound shape.

(319) The role of central sensitization in pain hypersensitivity in individuals with symptoms of migraine headache

Repeated migraine attacks are associated with maladaptive neural plasticity and lead to chronic headache. Sensitization of the pain pathways could play an important role in migraine’s pathophysiology and in the transition to the chronic forms of the disorder. In a previous study our laboratory found that subjects with a history of adverse childhood events presented a significantly increased area of capsaicin-induced secondary hyperalgesia, a measure of central sensitization, suggesting that exposure to trauma dysregulates neurogenic inflammation and pain modulatory systems. In addition, results from a recent study suggest that exposure to maltreatment can induce oxytocin dysregulation, which may also contribute to increased pain sensitivity. The goals of this study were to evaluate the differences in laboratory-induced pain and central sensitization between migraineurs and healthy controls. In addition, we explored whether childhood trauma and oxytocin levels mediate pain hypersensitivity. Thirty-three individuals with migraine headache and thirty-two healthy individuals underwent pain sensitivity testing following topical capsaicin application to the volar forearm. Childhood trauma, oxytocin levels and psychological measures were also assessed. We observed a significant increase in the area of secondary hyperalgesia (p=0.019) as well as capsaicin-induced unpleasantness (p=0.018) in migraineurs compared to healthy controls. However, no significant difference in oxytocin levels (p=0.110; Mann-Whitney U-test) and reported childhood traumatic events (p=0.055; Mann-Whitney U-test) were found between groups.

カプサイシンを用いた舌痛症モデルにおける舌の疼痛閾値の検討

カプサイシンを用いた舌痛症モデルにおける舌の疼痛閾値の検討

An investigation of the neural mechanisms underlying the efficacy of the adjustable gastric band

BackgroundThe mechanisms via which adjustable gastric band (AGB) surgery provides effective and durable weight loss remain unclear. ObjectivesThis study defines the role of sensory vagal fibers in the efficacy of the adjustable gastric banding using capsaicin to eliminate unmyelinated afferent fibers in the vagus nerve in a rodent model. SettingUniversity. MethodsA miniaturized AGB was fitted at the gastroesophageal junction of obese rats with either intact or sensory fiber depleted vagus nerves where deafferentation involved intraperitoneal (125 mg/kg) or topical (1% to the stomach) application of capsaicin. The extent of sensory fiber lesion was assessed using c-fiber-mediated reduction in cholecystokinin-induced feeding. Food intake, weight, and composition, as well as shifts in central neural activity (measured by elevation of Fos protein), were assessed after either control or AGB inflation with or without vagal deafferentation. ResultsAGB inflation caused a significant reduction in food intake, weight, and fat mass (P<.05) in obese rats. The effect of AGB on these parameters was prevented in capsaicin pretreated (vagal sensory lesioned) rats. Elevations in neural activity in the nucleus of the solitary tract and parabrachial nucleus after AGB inflation were ameliorated in capsaicin-treated rats. ConclusionVagal sensory fibers are integral to the efficacy of the AGB.

Spatial and Temporal Effects of Capsaicin and Menthol on Intraoral Somatosensory Sensitivity

To assess the spatial and temporal sensory effects of the topical application of capsaicin and menthol on the gingiva of healthy volunteers. Capsaicin, menthol, and saline (control) were applied topically on the gingiva in the maxillary premolar area of healthy volunteers for 15 minutes. Pain intensity was rated on a 0 to 10 visual analog scale (VAS). Before, immediately after, and 30 minutes after application, three mechanical stimuli were applied at 15 gingival sites: fixed-intensity stimuli were applied by 32 mN and 512 mN von Frey filaments, and stimuli of increasing intensity were applied by an electronic von Frey (EVF, 10 g/s). The EVF was used to test the pinprick pain threshold (PiPT). The perceived pain from filament stimulation was rated on a 0-50-100 numeric rating scale (NRS). Analysis of variance for repeated measures was used to analyze the NRS scores, PiPT values, the number of hypersensitive or hyposensitive test sites, and the coordinates of the center of gravity (COG) of somatosensory sensitivity. The mean ± SEM VAS score of pain intensity produced by the application of capsaicin (4.6 ± 0.5) was significantly higher than that produced by menthol (0.3 ± 0.2) and saline (0.1 ± 0.1) (P < .001). Capsaicin induced local desensitization to all stimuli (P < .047) , and at the application site, capsaicin induced significant desensitization to 512 mN stimuli (P = .003). Menthol did not induce significant somatosensory changes (P > .147), and saline induced slight desensitization in two sites surrounding the application site (P < .023). The COG coordinates did not shift significantly over time during any condition (P > .125). Capsaicin but not menthol induced mechanical desensitization in the application area but not in the surrounding areas.

Pereskia aculeata Miller leaves present in vivo topical anti-inflammatory activity in models of acute and chronic dermatitis

Ethnopharmacological relevance: The leaves of Pereskia aculeata Miller (Cactaceae), known as Barbados gooseberry, are used in Brazilian traditional medicine as emollients and to treat skin wounds and inflammation. This study investigated the topical anti-inflammatory activity of the hexane fraction (HF) obtained from the methanol extract of the leaves of this species in models of acute and chronic ear dermatitis in mice.Material and methods: Mice ear edema was induced by topical application of croton oil, arachidonic acid, capsaicin, ethyl-phenylpropiolate and phenol; and by subcutaneous injection of histamine. Ear biopsies were obtained to determine the levels of IL-1β, IL-6 and TNF-α cytokines by ELISA assay. Histopathological analysis was also performed to evaluate the HF activity in croton oil multiple application test. In addition, acute dermal irritation/corrosion test in rats was accomplished. HF chemical characterization was performed by GC–MS analysis.Results: HF intensively reduced the inflammatory process induced by all irritant agents used, except for arachidonic acid. This activity is related, at least in part, to the reduction of IL-6 and TNF-α cytokines levels. Moreover, when the glucocorticoid receptor antagonist mifepristone was used, HF failed to respond to the croton oil application.The results strongly suggested a glucocorticoid-like effect, which was reinforced by the presence of considerable amounts of sterol compounds identified in HF. The acute dermal irritaton/corrosion test showed no signs of toxicity.Conclusions: This study showed that the acute and chronic anti-inflammatory activity of P. aculeata leaves is very promising, and corroborates to better understand their ethnopharmacological applications.

A More Pessimistic Life Orientation Is Associated With Experimental Inducibility of a Neuropathy-like Pain Pattern in Healthy Individuals

The clinical pattern of neuropathic pain, diagnosed using the quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain), could be partly mimicked in healthy volunteers after topical capsaicin application. However, similar to clinical neuropathic pain that develops in only a subgroup of patients who have a neurologic lesion, this attempt to mimick a neuropathic pain pattern succeeded only in a small fraction (18%) of healthy individuals. In the present assessment, we pursued the hypothesis that the inducible subgroup differed from the other healthy participants with respect to their psychological phenotype. Therefore, in an observational study, participants were assessed using a comprehensive set of psychological variables comprising general psychological and pain-related cognitive-emotional mechanisms. The sum scores of the questionnaires were significantly linearly correlated with each other. Principal component analysis indicated that a major source of variance (46%) could be attributed to dispositional optimism examined via the Life Orientation Test (LOT). The LOT score significantly differed between the groups of participants, either those in whom a neuropathy-like pattern of pain assessed via QST could be partly (50–60% of the 11 QST parameters) induced (n = 20) or not (n = 90; P = .0375). It emerged again as the main selection criterion in a classification and regression tree predicting a participant's group assignment (inducible neuropathy-like QST pattern versus noninducible neuropathy-like QST pattern) at a cross-validated accuracy of 95.5 ± 2.1%. Thus, the few participants in a random sample of healthy volunteers who, after topical capsaicin application, partly resemble (to a degree of about 60%) the clinical pattern of neuropathic pain in the QST test battery, are preselectable on the basis of psychological factors, with a particular emphasis on pessimistic life attitudes. PerspectiveIn a small fraction of 18% of healthy volunteers, topical capsaicin application resulted in a neuropathy-like pattern in 50 to 60% of the components of a clinical test battery. These individuals displayed a more pessimistic life attitude as assessed by means of the LOT.

Altered thermal grill response and paradoxical heat sensations after topical capsaicin application.

The thermal grill illusion, where interlaced warm and cold bars cause an unusual burning sensation, and paradoxical heat sensations (PHS), where cold is perceived as warm when alternating warm and cold, are examples of a complex integration of thermal sensations. Here, we investigated the effect of sensitization of heat-sensitive neurons on cold and warm integration. We examined thermal thresholds, PHS, and warm, cold, and pain sensations to alternating cold (10°C) and warm (40°C) bars (the thermal grill [TG]) in the primary area (application site) after topical application with capsaicin and vehicle control (ethanol) on the volar forearms in randomized order in 80 healthy participants. As expected, capsaicin induced heat allodynia and hyperalgesia and decreased cold and cold pain sensation. In addition, we found that after capsaicin application, the TG caused less pain and burning than the 40°C bars alone in contrast to the control side where the TG caused more pain and burning, consistent with the thermal grill illusion. In both situations, the pain intensity during the TG correlated inversely with both cold and warm pain thresholds but not with detection thresholds. Paradoxical heat sensation was only seen in 3 participants after control application but in 19 participants after capsaicin. Those with PHS after capsaicin application had higher detection thresholds to both cold and warm than those without PHS, but there was no difference in thermal pain threshold. These results suggest that a complex cross talk among several cold and warm sensitive pathways shapes thermal perception.

Effectiveness of High-Frequency Electrical Stimulation Following Sensitization With Capsaicin

Although nonnoxious, high-frequency electrical stimulation applied segmentally (ie, conventional transcutaneous electrical nerve stimulation [TENS]) has been proposed to modulate pain, the mechanisms underlying analgesia remain poorly understood. To further elucidate how TENS modulates pain, we examined evoked responses to noxious thermal stimuli after the induction of sensitization using capsaicin in healthy volunteers. We hypothesized that sensitization caused by capsaicin application would unmask TENS analgesia, which could not be detected in the absence of sensitization. Forty-nine healthy subjects took part in a series of experiments. The experiments comprised the application of topical capsaicin (.075%) on the left hand in the C6 dermatome, varying the location of TENS (segmental, left C6 dermatome, vs extrasegmental, right shoulder), and assessing rating of perception (numeric rating scale: 0–10) and evoked potentials to noxious contact heat stimuli. The extrasegmental site was included as a control condition because previous studies indicate no analgesic effect to remote conventional TENS. Conventional TENS had no significant effect on rating or sensory evoked potentials in subjects untreated with capsaicin. However, segmental TENS applied in conjunction with capsaicin significantly reduced sensation to noxious thermal stimuli following a 60-minute period of sensitization. PerspectiveThe study indicates that sensitization with capsaicin unmasks the analgesic effect of conventional TENS on perception of noxious contact heat stimuli. Our findings indicate that TENS may be interacting segmentally to modulate distinct aspects of sensitization, which in turn results in analgesia to thermal stimulation.

Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice

Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice.

The efficacy of capsaicin as an equine repellent for chewing wood

Capsaicin, a component of chili peppers, is a natural repellent for many mammals because of it being an irritant to the nasal and oral areas. We tested whether topical application of capsaicin in a commercially available product caused aversion to licking and chewing of wood by horses and hence might potentially prevent crib biting. Ten non–wood-chewing horses underwent 3 sequential trials involving the presentation of different treatments applied to a clean piece of wood (wooden block). Initially horses were exposed to molasses only, followed by equal proportions of molasses and the capsaicin product (Equi-Stop), and then a return to molasses only. The addition of capsaicin to molasses caused a significant reduction in the frequency of licking or chewing of a standardized wooden block and was associated with significant increases in behaviors that may be associated with equine irritation, including rubbing and head shaking, plus the nasal investigative behavior of flehmen response. The combination of both the reduction of licking or chewing of the wooden block and the increase in irritation and nasal investigation behaviors suggests that capsaicin may be an effective repellent for horses chewing wood. The significantly lower licking or chewing rates of wooden blocks coated with molasses only at the end of the trial sequence compared to that at the start suggests a learned aversion after exposure to capsaicin at least in some horses. This capsaicin-based product has the potential as a management tool for reducing the incidence of wood chewing and possibly crib biting in horses.

Management of Neuropathic Pain Associated with Spinal Cord Injury.

Spinal cord injury (SCI) is an injury to the spinal cord that leads to varying degrees of motor and/or sensory deficits and paralysis. Chronic pain of both neuropathic and nociceptive type is common and contributes to reduced quality of life. The aim of the review is to provide current clinical understanding as well as discuss and evaluate efficacy of pharmacological interventions demonstrated in the clinical studies. The review was based on literature search in PubMed and Medline with words “neuropathic pain” and “spinal cord injury”. The review included clinical studies and not experimental data nor case reports. A limited number of randomized and placebo-controlled studies concerning treatment options of neuropathic pain after SCI were identified. Amitriptyline, a tricyclic antidepressant and the antiepileptic drugs, gabapentin and pregabalin, are most studied with demonstrated efficacy, and considered to be the primary choice. Opioids have demonstrated conflicting results in the clinical studies. In addition, administration route used in the studies as well as reported side effects restrict everyday use of opioids as well as ketamine and lidocaine. Topical applications of capsaicin or lidocaine as well as intradermal injections of Botulinum toxin are new treatment modalities that are so far not studied on SCI population and need further studies. Non-pharmacological approaches may have additional effect on neuropathic pain. Management of pain should always be preceded by thorough clinical assessment of the type of pain. Patients need a follow-up to evaluate individual effect of applied measures. However, the applied management does not necessarily achieve satisfactory pain reduction. Further clinical studies are needed to evaluate the effect of both established and novel management options.

Pattern of neuropathic pain induced by topical capsaicin application in healthy subjects.

Human experimental pain models are widely used to study drug effects under controlled conditions, but they require further optimization to better reflect clinical pain conditions. To this end, we measured experimentally induced pain in 110 (46 men) healthy volunteers. The quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain) was applied on untreated ("control") and topical capsaicin-hypersensitized ("test") skin. Z-transformed QST-parameter values obtained at the test site were compared with corresponding values published from 1236 patients with neuropathic pain using Bayesian statistics. Subjects were clustered for the resemblance of their QST pattern to neuropathic pain. Although QST parameter values from the untreated site agreed with reference values, several QST parameters acquired at the test site treated with topical capsaicin deviated from normal. These deviations resembled in 0 to 7 parameters of the QST pattern observed in patients with neuropathic pain. Higher degrees (50%-60%) of resemblance to neuropathic QST pattern were obtained in 18% of the subjects. Inclusion in the respective clusters was predictable at a cross-validated accuracy of 86.9% by a classification and regression tree comprising 3 QST parameters (mechanical pain sensitivity, wind-up ratio, and z-transformed thermal sensory limen) from the control sites. Thus, we found that topical capsaicin partly induced the desired clinical pattern of neuropathic pain in a preselectable subgroup of healthy subjects to a degree that fuels expectations that experimental pain models can be optimized toward mimicking clinical pain. The subjects, therefore, qualify for enrollment in analgesic drug studies that use highly selected cohorts to enhance predictivity for clinical analgesia.

Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review

Capsaicin, the pungent alkaloid of red pepper (Capsicum annuum) has been extensively studied for its biological effects which are of pharmacological relevance. These include: cardio protective influence, antilithogenic effect, antiinflammatory, and analgesia, thermogenic influence, and beneficial effects on gastrointestinal system. Therefore, capsaicinoids may have the potential clinical value for pain relief, cancer prevention and weight loss. It has been shown that capsaicinoids are potential agonists of capsaicin receptor (TRPV1). They could exert the effects not only through the receptor-dependent pathway but also through the receptor-independent one. The involvement of neuropeptide Substance P, serotonin, and somatostatin in the pharmacological actions of capsaicin has been extensively investigated. Topical application of capsaicin is proved to alleviate pain in arthritis, postoperative neuralgia, diabetic neuropathy, psoriasis, etc. Toxicological studies on capsaicin administered by different routes are documented. Capsaicin inhibits acid secretion, stimulates alkali and mucus secretion and particularly gastric mucosal blood flow which helps in prevention and healing of gastric ulcers. Antioxidant and antiinflammatory properties of capsaicin are established in a number of studies. Chemopreventive potential of capsaicin is evidenced in cell line studies. The health beneficial hypocholesterolemic influence of capsaicin besides being cardio protective has other implications, viz., prevention of cholesterol gallstones and protection of the structural integrity of erythrocytes under conditions of hypercholesterolemia. Beneficial influences of capsaicin on gastrointestinal system include digestive stimulant action and modulation of intestinal ultrastructure so as to enhance permeability to micronutrients.