Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C

Fehrenbacher, Jill C.; Taylor, Charles P.; Vasko, Michael R.

doi:10.1016/s0304-3959(03)00173-8

Cited by 299 publications

(178 citation statements)

References 54 publications

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“…28 Peripherally-released substance P and CGRP were noted to mediate mechanical hyperalgesia in a peripheral neuropathic pain model. 29 Therefore, pregabalin administered peripherally may affect the release of these mediators and alleviate the hyperalgesia in this type of pain model.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of neuropathy-induced allodynia following intraplantar injection of pregabalin

Park

Joo

Chang

et al. 2010

Can J Anesth/J Can Anesth

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Purpose Pregabalin exhibits potent anticonvulsant, analgesic, and anxiolytic activity in animal models. However, few studies have evaluated pregabalin's potential peripheral effects on neuropathic pain. The aim of this study was to evaluate the peripheral analgesic effects of pregabalin in a rat model of neuropathic pain. Methods Male Sprague-Dawley rats were prepared by ligating the left L5 and L6 spinal nerves to produce neuropathic pain. Sixty rats with neuropathic pain were randomly assigned to six groups. Normal saline (control) and pregabalin (10,20,30, and 50 mgÁkg -1 ) were administered to the plantar surface of the affected left hind paw. Pregabalin (50 mgÁkg -1 ) was administered into the unaffected contralateral paw in order to determine its systemic effect. Responses to mechanical, cold, and heat stimulation were recorded at 15,30, 60, 90, 120, 150, and 180 min after drug administration. Rotarod performance was measured to detect drug-induced side effects, including sedation and reduced motor coordination. Results Saline injected into the affected paw and a pregabalin dose of 50 mgÁkg -1 injected into the contralateral paw showed no differences for mechanical, cold, and heat allodynia. Administration of pregabalin to the affected left hind paw in the dose range of 10-50 mgÁkg -1 resulted in a dose-dependent increase in thresholds to mechanical, cold, and heat stimulation. Conclusion Peripherally administered pregabalin attenuates mechanical, cold, and heat allodynia in a rat model of neuropathic pain. RésuméObjectif La pre´gabaline de´montre une puissante activiteá nticonvulsivante, analge´sique et anxiolytique dans les mode`les animaux. Ne´anmoins, il n'existe que peu d'e´tudes ayant e´value´les effets pe´riphe´riques potentiels de la pre´gabaline sur la douleur neuropathique. L'objectif de cette e´tude e´tait d'examiner les effets analge´siques pe´riphe´riques de la pre´gabaline dans un mode`le de douleur neuropathique chez le rat. Méthode Des rats Sprague-Dawley maˆles ont e´teṕ re´pare´s en ligaturant les nerfs rachidiens L5 et L6 afin de cre´er une douleur neuropathique. Soixante rats souffrant de douleur neuropathique ont e´te´ale´atoirement re´partis en six groupes. Du se´rum physiologique (te´moin) et de la pre´gabaline (10, 20, 30, et 50 mgÁkg -1 ) ont e´te´administre´s a`la surface plantaire de la patte arrie`re gauche affecte´e. De la pre´gabaline (50 mgÁkg -1 ) a e´te´administre´e à la patte controlate´rale non affecte´e afin de de´terminer son effet syste´mique. Les re´actions aux stimulations me´caniques, au froid et a`la chaleur ont e´te´enregistre´es a1 5, 30, 60, 90, 120, 150 et 180 min apre`s l'administration du me´dicament. La performance au test de la tige tournante a e´te´mesure´e afin de de´pister les effets secondaires provoque´s par le me´dicament, notamment la se´dation et une re´duction de la coordination motrice.This article is accompanied by an editorial. Please see Can J Anesth 2010; 57(7).

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Section: Discussionmentioning

confidence: 99%

Attenuation of neuropathy-induced allodynia following intraplantar injection of pregabalin

Park

Joo

Chang

et al. 2010

Can J Anesth/J Can Anesth

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“…Its chemical structure is similar to GABA, but it does not act like GABA, and in particular, does not bind to GABA receptor. Moreover, GP is known to potently bind to the a2-d subunit of voltage-controlled calcium channels, and its binding at this site reduces Ca 2+ influx at presynaptic nerve endings and therefore, reduces the release of several neurotransmitters, which included glutamate and noradrenalin [3,9,11,21]. Given this theoretical background, we wondered whether GP might act as a neuroprotector after SCI, and thus we examined the possibility that GP acts as has a neuroprotective agents.…”

Section: Discussionmentioning

confidence: 99%

Pregabalin as a neuroprotector after spinal cord injury in rats

Kim

Rhyu

et al. 2008

Eur Spine J

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The over-expression of excitotoxic neurotransmitter, such as glutamate, is an important mechanism of secondary injury after spinal cord injury. The authors examined the neuroprotective effect of pregabalin (GP) which is known as to reduce glutamate secretion, in a rat model of spinal cord injury. Thirty-two male SpragueDawley rats were randomly allocated to four groups; the control group (contusion injury only), the methylprednisolone treated group, the minocycline treated group and the GP treated group. Spinal cord injury was produced by contusion using the New York University impactor (25 gcm, at the 9th-10th thoracic). Functional evaluations were done using the inclined plane test and a motor rating scale. Anti-apoptotic and anti-inflammatory effects were evaluated by in situ nick-end labeling staining technique (TUNEL) and immunofluorescence staining of cord tissues obtained at 7 days post-injury. Pregabalin treated animals showed significantly better functional recovery, and antiapoptotic and anti-inflammatory effects. Mean numbers of TUNEL positive cells in the respective groups were 63.5 ± 7.4, 53.6 ± 4.0, 44.2 ± 3.9 and 36.5 ± 3.6. Double staining (TUNEL and anti-CC1) for oligodendrocyte apoptosis, was used to calculate oligodendrocyte apoptotic indexes (AI), using the following formula AI = (No. of doubly stained cells/No. of anti-CC1 positive cells) 9 100.Mean group AIs were 88.6, 46.7, 82.1 and 70.3%, respectively. Mean numbers of activated microglia (anti-OX-42 positive cells) in high power fields were 29.8 ± 3.9, 22.7 ± 4.1, 21.0 ± 3.9 and 17.8 ± 4.3, respectively. This experiment demonstrates that GP can act as a neuroprotector after SCI in rats, and its anti-apoptotic and anti-inflammatory effects are related to its neuroprotective effect. Further studies are needed to unveil the specific mechanism involved at the receptor level.

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“…Gabapentin has proved an anti-inflammatory effect in animal model (19,20). In human, Werner's study showed gabapentin reduces primary mechanical allodynia in acute inflammation following a thermal injury (21).…”

Section: Panah Khahi M Et Almentioning

confidence: 99%

Postoperative Gabapentin to Prevent Postoperative Pain: A Randomized Clinical Trial

Khahi¹,

Marashi²,

Khajavi³

et al. 2012

anesthpain

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Gabapentin is an anticonvulsant that has postoperative analgesic effects but there have been limited studies on its postoperative administration. The present study was conducted to evaluate the effect of the postoperative oral gabapentin on pain and morphine consumption. The results indicated no significant analgesic efficacy of oral gabapentin 300 mg immediately after tibia internal fixation surgery under spinal anesthesia at time points of 2, 12 and 24 hours postoperatively. 4). Gabapentin has an analgesic (5) and opioid-sparing effect (1, 4, 6) both at rest and with movement (7) in acute postoperative pain management (1,(8)(9)(10)(11)(12)(13). Postoperative pain is not purely nociceptive and may have other (inflammatory and visceral) components (14); so using drugs that act on different analgesic mechanisms seems BackgroundNowadays, a variety of new drugs, devices, analgesic techniques and preventive approaches are available for anesthesiologists including patient-controlled analgesia, multimodal analgesia and pre-emptive analgesia (1-Background: Gabapentin is an anticonvulsant that has postoperative analgesic effects but there are limited studies on its postoperative administration. Objectives: The present study was conducted to evaluate the effect of the postoperative oral gabapentin on pain and morphine consumption. Patients and Methods:In a double blind, randomized study, 64 patients undergoing internal fixation of tibia under spinal anesthesia were randomly assigned to receive oral gabapentin or placebo immediately after the surgery. Pain scores were recorded at time points of 2, 12 and 24 hours postoperatively using visual analog scale (VAS). Time duration from the end of surgery until morphine administration and total morphine requirement in the first 24 hours were recorded. Results: The estimated duration of surgeries was 120-150 minutes. VAS score was not significantly different between the two groups at 2, 12 and 24 hours after surgery. There was no significant morphine consumption difference between the groups. Conclusions: Our study showed no significant analgesic efficacy of oral gabapentin 300 mg immediately after tibia internal fixation surgery under spinal anesthesia at time points of 2, 12 and 24 hours postoperatively.

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Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C

Cited by 299 publications

References 54 publications

Attenuation of neuropathy-induced allodynia following intraplantar injection of pregabalin

Attenuation of neuropathy-induced allodynia following intraplantar injection of pregabalin

Pregabalin as a neuroprotector after spinal cord injury in rats

Postoperative Gabapentin to Prevent Postoperative Pain: A Randomized Clinical Trial

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