Clinical use of pregabalin in the management of central neuropathic pain

Central neuropathic pain (central pain) is treated with antidepressants, various anticonvulsants, opioids, and cannabinoids, but in many cases treatment is insufficient and associated with a range of side-effects. This review addresses a new treatment for neuropathic pain, the anticonvulsant pregabalin. We review the pharmacology, mode of action, pharmacokinetics, and safety of pregabalin as well as two randomized efficacy studies in central pain and a brief overview of efficacy in peripheral neuropathic pain. Pregabalin appears to have efficacy in treating central pain comparable to that in peripheral neuropathic pain as well as efficacy of other recommended drugs for central pain. Pregabalin also improves disturbed sleep and anxiety. Pregabalin is well tolerated; the most common side-effects are somnolence, dizziness, ataxia, and weight gain. Pregabalin is suitable for patients on multiple drugs although there may be additive CNS-related side-effects. Thus, pregabalin has a primary role in central pain patients

Trigeminal neuralgia: new classification and diagnostic grading for practice and research

Trigeminal neuralgia (TN) is an exemplary condition of neuropathic facial pain. However, formally classifying TN as neuropathic pain based on the grading system of the International Association for the Study of Pain is complicated by the requirement of objective signs confirming an underlying lesion or disease of the somatosensory system. The latest version of the International Classification of Headache Disorders created similar difficulties by abandoning the term symptomatic TN for manifestations caused by major neurologic disease, such as tumors or multiple sclerosis. These diagnostic challenges hinder the triage of TN patients for therapy and clinical trials, and hamper the design of treatment guidelines. In response to these shortcomings, we have developed a classification of TN that aligns with the nosology of other neurologic disorders and neuropathic pain. We propose 3 diagnostic categories. Classical TN requires demonstration of morphologic changes in the trigeminal nerve root from vascular compression. Secondary TN is due to an identifiable underlying neurologic disease. TN of unknown etiology is labeled idiopathic. Diagnostic certainty is graded possible when pain paroxysms occur in the distribution of the trigeminal nerve branches. Triggered paroxysms permit the designation of clinically established TN and probable neuropathic pain. Imaging and neurophysiologic tests that establish the etiology of classical or secondary TN determine definite neuropathic pain

Delta and gamma oscillations in operculo-insular cortex underlie innocuous cold thermosensation

Cold-sensitive and nociceptive neural pathways interact to shape the quality and intensity of thermal and pain perception. Yet the central processing of cold thermosensation in the human brain has not been extensively studied. Here, we used magnetoencephalography and EEG in healthy volunteers to investigate the time course (evoked fields and potentials) and oscillatory activity associated with the perception of cold temperature changes. Nonnoxious cold stimuli consisting of Δ3°C and Δ5°C decrements from an adapting temperature of 35°C were delivered on the dorsum of the left hand via a contact thermode. Cold-evoked fields peaked at around 240 and 500 ms, at peak latencies similar to the N1 and P2 cold-evoked potentials. Importantly, cold-related changes in oscillatory power indicated that innocuous thermosensation is mediated by oscillatory activity in the range of delta (1–4 Hz) and gamma (55–90 Hz) rhythms, originating in operculo-insular cortical regions. We suggest that delta rhythms coordinate functional integration between operculo-insular and frontoparietal regions, while gamma rhythms reflect local sensory processing in operculo-insular areas

Fatty acid suppression of glial activation prevents central neuropathic pain after spinal cord injury

Supplemental digital content associated with this article can be found online at http://links.lww.com/PAIN/A853Peer reviewedPostprin

Electroencephalographic predictors of neuropathic pain in subacute spinal cord injury

It is widely believed that cortical changes are a consequence of long standing neuropathic pain (NP). In this paper we demonstrate that NP in people with subacute spinal cord injury (SCI) has characteristic electroencephalographic (EEG) markers which precede the onset of pain. EEG was recorded in a relaxed state and during motor imagination tasks in 10 able bodied participants and 31 subacute SCI participants (11 with NP, 10 without NP and 10 who developed pain within 6 months of EEG recording). All 20 SCI participants initially without NP were tested for mechanically induced allodynia but only one person, who later developed pain, reported an unpleasant sensation. The EEG reactivity to opening eyes was reduced in the alpha band and absent in the theta and beta bands in participants who later developed pain, and it was reduced in participants who already had pain. Alpha band power was reduced at BA7 in both the relaxed state and during motor imagination in participants who either had or later developed pain compared to participants without pain. All SCI groups had reduced dominant alpha frequency and beta band power at BA7. Electroencephalographic reactivity to eyes opening, and reduced spontaneous and induced alpha activity over the parietal cortex were predictors of future NP as well as markers of existing NP. Clinical Trial Registration Number: NCT02178917 Perspectives: We demonstrate that brain activity in subacute SCI contains both early markers and predictors of NP, which may manifest before sensory discomfort. These markers and predictors may complement known sensory phenotypes of NP. They may exist in other patient groups suffering from NP of central origin

Pain Following Stroke: A Population-Based Follow-Up Study

Background and Purpose: Chronic pain is increasingly recognized as a consequence of stroke. This study aimed to describe the prevalence and pain types of new onset chronic pain (‘‘novel pain’’) in patients with stroke compared with a randomly selected reference group from the general population and to identify factors associated with pain development in stroke patients. Methods: In a population-based follow-up design, development of chronic pain after stroke was assessed by a questionnaire sent to consecutive stroke patients, registered in a Danish national stroke database, two years after their stroke. A randomly selected sex- and age-matched reference group from the same catchment area received a similar questionnaire about development of new types of chronic pain in the same time period. A total of 608 stroke patients and 519 reference subjects were included in the study. Results: Development of novel pain was reported by 39.0 % of stroke patients and 28.9 % of reference subjects (OR 1.57, CI 1.21-2.04), and was associated with low age and depression in a multivariate model. Daily intake of pain medication for novel pain was reported by 15.3 % and 9.4 % of the stroke and reference population, respectively. Novel headache, shoulder pain, pain from increased muscle stiffness, and other types of novel pain were more common in stroke patients, whereas joint pain was equally common in the two groups. Conclusions: Development of chronic pain is more common in stroke patients compared with sex- and age-matched reference subjects. Evaluation of post-stroke pain should be part of stroke follow-up