Systemic gabapentin and S(+)-3-isobutyl-γ-aminobutyric acid block secondary hyperalgesia

Jones, D. R.; Sorkin, Linda S.

doi:10.1016/s0006-8993(98)00890-7

Cited by 99 publications

(48 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although pregabalin does interact with the same binding site and has a similar pharmacologic profile as gabapentin [16], its binding affinity for the a2-d subunit, and potency, is six times more than that of gabapentin [27]. Furthermore, orally administered pregabalin is absorbed more rapidly than gabapentin, with maximum plasma concentrations attained within 1 h as opposed to 3-4 h [15].…”

Section: Pregabalin Vs Gabapentinmentioning

confidence: 99%

Misuse and Abuse of Pregabalin and Gabapentin: Cause for Concern?

2014

View full text Add to dashboard Cite

Gabapentinoids (e.g. pregabalin and gabapentin) are widely used in neurology, psychiatry and primary healthcare but are increasingly being reported as possessing a potential for misuse. In fact, increasing levels of both prescriptions and related fatalities, together with an anecdotally growing black market, have been reported from a range of countries. This article reviews the current evidence base of this potential, in an attempt to answer the question of whether there is cause for concern about these drugs. Potent binding of pregabalin/gabapentin at the calcium channel results in a reduction in the release of excitatory molecules. Furthermore, gabapentinoids are thought to possess GABA-mimetic properties whilst possibly presenting with direct/indirect effects on the dopaminergic 'reward' system. Overall, pregabalin is characterized by higher potency, quicker absorption rates and greater bioavailability levels than gabapentin. Although at therapeutic dosages gabapentinoids may present with low addictive liability levels, misusers' perceptions for these molecules to constitute a valid substitute for most common illicit drugs may be a reason of concern. Gabapentinoid experimenters are profiled here as individuals with a history of recreational polydrug misuse, who self-administer with dosages clearly in excess (e.g. up to 3-20 times) of those that are clinically advisable. Physicians considering prescribing gabapentinoids for neurological/psychiatric disorders should carefully evaluate a possible previous history of drug abuse, whilst being able to promptly identify signs of pregabalin/gabapentin misuse and provide possible assistance in tapering off the medication. Key pointsGabapentinoids are thought to possess GABAmimetic properties, whilst possibly presenting with direct/indirect effects on the dopaminergic 'reward' system.Gabapentinoid experimenters are profiled here as individuals with a history of recreational polydrug misuse, who self-administer with dosages clearly in excess (e.g. up to 3-20 times) of those that are clinically advisable.Physicians considering prescribing gabapentinoids for neurological/psychiatric disorders should carefully evaluate for a possible previous history of drug abuse, whilst being able to promptly identify signs of pregabalin/gabapentin misuse and provide possible assistance in tapering off the medication.

show abstract

Section: Pregabalin Vs Gabapentinmentioning

confidence: 99%

Misuse and Abuse of Pregabalin and Gabapentin: Cause for Concern?

2014

View full text Add to dashboard Cite

show abstract

“…A dissociation between the size of antinociceptive and antihyperalgesic effects of gabapentin is also supported by other studies. Behavioral and electrophysiological experiments in animals show that gabapentin has minor modulatory effects on acute nociception, but it produces a robust dose-dependent inhibition of allodynia and hyperalgesia in different models of central sensitization (12,13,16,50). In humans, gabapentin does not increase thermal and mechanical pain thresholds (51) or tolerance to cold pressure test (17), but it reduces stroking and punctate hyperalgesia in experimental central sensitization (18,52).…”

Section: Gabapentin Modulation Of Fmri Brain Responses: Antihyperalgesicmentioning

confidence: 99%

Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans

Iannetti

Zambreanu

Wise

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

253

203

View full text Add to dashboard Cite

Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.deactivation ͉ fMRI ͉ hyperalgesia ͉ nociceptive system A fter skin injury, an increased sensitivity to mechanical stimuli occurs in a large, uninjured area surrounding the injury site (1, 2). This phenomenon is termed secondary hyperalgesia and is the consequence of neuroplastic changes leading to a state of sensitization of the central nervous system (central sensitization) (3). Secondary hyperalgesia can be experimentally induced by treating the skin with high doses of the vanilloid capsaicin (by intradermal injection or topical application).Two forms of mechanical hyperalgesia occur in the area of secondary hyperalgesia: hyperalgesia to gentle skin stroking (stroking hyperalgesia or allodynia) and hyperalgesia to punctate stimuli (punctate hyperalgesia). Although both stroking and punctate hyperalgesia are due to central sensitization, they have different psychophysical characteristics (punctate hyperalgesia is easier to establish, it encompasses a larger area and it is longer-lasting than stroking hyperalgesia). They are mediated by different primary afferents (3): stroking hyperalgesia is signaled by low-threshold mechanoreceptors (4), whereas punctate hyperalgesia is signaled by capsaicin-insensitive A-fi...

show abstract

“…2 Gabapentin (GBP) is an anticonvulsant that is also used for the treatment of pain 3,11,12,16 and anxiety. 16,19 Gabapentin is not bound to plasma proteins and is not metabolized in humans, being excreted unchanged in urine.…”

mentioning

confidence: 99%