Pregabalin in the Treatment of Chronic Pain

Abstract

Chronic 'pathological' pain is sustained by mechanisms of peripheral and central sensitization, which are being increasingly investigated at the molecular and cellular levels. The molecular determinants of nociceptive sensitization are natural targets for potential analgesic drugs used in the treatment of different forms of pain. Most of these determinants are common to all forms of chronic pain, and it is therefore not surprising that drugs specifically targeted for the treatment of neuropathic pain are effective in relieving nociceptive inflammatory pain and vice versa. The molecular mechanisms of sensitization that occur in peripheral nociceptors and the dorsal horns of the spinal cord are putative targets for context-dependent drugs, i.e. drugs that are able to discriminate between 'normal' and 'pathological' pain transmission. Among these, pregabalin and gabapentin bind to the alpha(2)delta subunit of voltage-sensitive Ca2+ channels, which sustain the enhanced release of pain transmitters at the synapses between primary afferent fibres and second-order sensory neurons under conditions of chronic pain. Pregabalin in particular represents a remarkable example of a context-dependent analgesic drug that acts at a critical step of nociceptive sensitization. Preclinical and clinical data suggest that pregabalin is more than a structural and functional analogue of gabapentin and may be effective in the treatment of nociceptive inflammatory pain that is resistant to gabapentin.

Long-Term Controlled-Release Oxycodone and Pregabalin in the Treatment of Non-Cancer Pain: An Observational Study

“…Different molecular mechanisms involving peripheral and central sensitization sustain chronic pain [1]. However, most of these mechanisms are shared among the various forms of this condition [1].…”

Increased deep pain sensitivity in persistent musculoskeletal pain but not in other musculoskeletal pain states

“…Most patients in the persistent pain group received a mix of different pain-relieving drugs. These drugs could influence sensitization in persistent pain, for example, pregabalin and gabapentin reduce the sensitization elicited in the dorsal horn and in peripheral nociceptors [15]. According to this, the PPTs in the persistent pain group, were these medications existed could without these drugs have been even lower.…”

The use of pregabalin without prescription

“…Все это вызывает снижение высвобожде-ния моноаминов и активности натриевых каналов, уменьшение синтеза и транспорта возбуждающего нейромедиатора глутамата, что способствует умень-шению частоты потенциалов действия перифериче-ских нервов. Описанный механизм объясняет анальгетическую, противосудорожную и анксиоли-тическую активность прегабалина [10,11]. Благода-ря снижению выброса нейротрансмиттеров боли (включая глутамат, норадреналин и субстанцию Р), прегабалин селективно подавляет возбудимость се-ти нейронов, однако только при патологических со-стояниях [12].…”