Topical high-concentration menthol: reproducibility of a human surrogate pain model.

BACKGROUND: Human experimental pain models play an important role in studying neuropathic pain mechanisms. The objective of the present study was to test the reproducibility of the topical menthol model over a 1-week period. METHOD: We performed an open, two-period study in 10 healthy volunteers with 40 menthol applications. The side of menthol application was randomly assigned. Two trial periods were separated by 1 week. Before and after applying menthol, selected quantitative sensory testing (QST) was performed. The area of mechanical pin-prick hyperalgesia was quantified. Spontaneous pain was recorded. RESULTS: Application of menthol induced a statistically significant decrease in the cold pain threshold (CPT) (p < 0.001) and mechanical pain threshold and an increase in the mechanical pain sensitivity (MPS) (p < 0.001), indicating cold and mechanical (pin-prick) hyperalgesia. Test-retest reliability was best for CPT (r = 0.959) and MPS (r = 0.930). Intraclass correlation values showed excellent reliability for cold pain and MPS (ICC = 0.96, 0.89). The QST values post-menthol showed high inter-period correlation factors and no significant inter-period differences (paired t-test, t = 1.767-1.361; p = 0.111-0.988). The area size of mechanical hyperalgesia was not reliably reproducible. CONCLUSION: For an observation period of 1 week, the signs of cold and mechanical hyperalgesia were reproducible with a highly significant correlation of about r = 0.8 and good agreement except for the area size of mechanical pin-prick hyperalgesia. These results demonstrate that the topical menthol pain model is suitable for pharmacological interventions repeated within an observation period of 1 week.

Repetitive ipsilateral painful A-delta fibre stimuli induce bilateral LEP amplitude habituation.

BACKGROUND: In the scientific approach to central processing of pain, the habituation phenomenon has been frequently described. Recent studies mentioned electrophysiological habituation during the recording of laser-evoked potentials (LEP). In this study we intended to test whether habituation can be reproducibly induced by repetitive painful laser stimuli and simultaneously measured with LEP. Inspired by findings from previous imaging studies that showed bilateral activation of the operculo-insular cortices, we hypothesized that repetitive painful laser stimuli applied to one hand lead to bihemispheral LEP amplitude habituation. METHODS: One hundred painful stimuli were applied to the right hand of 13 healthy subjects to induce contralateral N2P2 amplitude habituation. The left hand was stimulated 25 times before and after the right-hand stimulation to measure ispilateral LEPs; the experiment was sham controlled. RESULTS: We achieved significant contralateral N2P2 amplitude and pain habituation in all subjects. After central habituation was established, there was also a significant ispilateral N2P2 amplitude decrement (derived from the left hand) compared with baseline; in the sham condition, the N2P2 amplitude was unchanged. The pain sensation showed no habituation in both the painful stimulation condition and the sham condition. CONCLUSIONS: Habituation (in the electrophysiological sense) is a physiological phenomenon that indicates normal central processing of pain in healthy controls. We showed bihemispheral N2P2 amplitude habituation after repetitive painful stimulation of the right hand. Our findings propose a bihemishperal contribution to central pain processing and pain modulation when electrophysiological habituation occurs.

[Types of topical treatment for peripheral neuropathic pain : Mechanism of action and indications]. / Topische Therapieformen bei peripheren neuropathischen Schmerzen : Wirkmechanismus und Indikationen.

The term "peripheral neuropathic pain syndromes" summarizes several chronic pain syndromes, which can occur focally or generalized in the peripheral nervous system in the course of an impairment of afferent neurons. Controlled clinical trials gave distinct indications for systemic treatments with antidepressants, anticonvulsants and opioid analgesics in several neuropathic pain syndromes. In addition to these systemic therapies, there are also two topical treatment options: topical application of lidocaine and capsaicin. An important cause of sensitization phenomena of afferent nociceptors is the upregulation of sodium channels and thermosensor channels. In the context of a partial nerve lesion that leaves behind partially preserved or regenerated afferent nerve fibres, just these channels could be used as target structures for topical medications. Topically applied drugs are absorbed systemically only in minute quantities, so systemic side effects are negligible. Pharmacological interactions with systematically acting substances are also virtually absent; thus, topically applied substances are especially appropriate for add-on therapy in addition to systemic pain medication.

[Postherpetic neuralgia]. / Postzosterische Neuralgie.

BACKGROUND: In the last years, new findings from the research on pain diseases and the enhancement of therapeutic options have drastically changed the treatment of postherpetic neuralgia (PHN). This disease, belonging to the neuropathic pain syndromes, needs an adequate pain therapy at an early stage to prevent pain chronicity. DEFINITION AND CLINICAL ATTRIBUTES OF PHN: In 20 % of all cases of herpes zoster, the innervation territory of the trigeminal nerve is affected. A PHN exists by definition in the case of persisting pain in the zoster-affected area 6 months after healing of the zoster eruptions. The incidence of PHN depends on the patient's age: 50 - 75 % of patients in the seventh decade develop PHN after an infection with herpes zoster. The clinical appearance of PHN is characteristic. Three different pain types can be distinguished: 1. spontaneous, constant, burning pain, 2. intermittent sharp, lancinating pain and 3. pain in response to a normally non-painful stimulus (mechanical allodynia). Other phenomena which can be observed are hyp- or anaesthesia, hypalgesia and par- or dysaesthesia. PATHOPHYSIOLOGY OF NEUROPATHIC PAIN: In the last few years, pathomechanisms of individual pain symptoms occurring in PHN have been identified. These include peripheral and central sensitisation as well as spontaneous activity of damaged afferent nociceptive fibres as the consequence of changes in channels on the neuron's membrane. TREATMENT OF PHN: A basic rule in the treatment of neuropathic pain syndromes is that the medication should be taken for at least 2 - 4 weeks before making a final evaluation. Systematic reviews of data from clinical trials of drug therapy for PHN have given distinct indications for antidepressants, antiepileptics, opioid analgesics and topically acting agents. Tricyclic antidepressants act on CNS pain-modulating descending pathways. The antiepileptics gabapentin and pregabalin act on calcium channels on presynaptic terminals of afferent nociceptive neurons in the central nervous system. Carbamazepine and oxcarbazepine may be helpful for some patients, but there is still a lack of controlled trials demonstrating efficacy in the treatment of PHN. Oral oxycodone and tramadol are verifiable effective drugs in PHN. Topically acting agents with verifiable efficacy in PHN are capsaicin and lidocaine, both available in the form of patches for local use.

High-pressure liquid chromatographic assay of folic acid: a collaborative study.

A collaborative study of the USP high-pressure liquid chromatographic assay for folic acid was performed. Two samples were analyzed in duplicate by 14 participating laboratories. Relative standard deviations for a single determination (RSDS) ranged from +/-0.40 to +/-2.39%. Based on an analysis of variance, it was concluded that the method of peak measurement was a major determinant of reproducibility and that graphical measurement was associated with a high standard deviation. Adequate resolution was obtained using a variety of columns and operating conditions. The interlaboratory RSDS was +/-1.8%.