An isobolographic analysis of drug interaction between intrathecal clonidine and baclofen in the formalin test in rats

Przesmycki, Krzysztof; Dzieciuch, Jacek A; Czuczwar, Stanisław J.; Kleinrok, Z

doi:10.1016/s0028-3908(98)00004-5

Cited by 18 publications

(4 citation statements)

References 42 publications

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“…Although baclofen is used clinically to treat neuropathic pain and, when administered intrathetically, to attenuate pain associated with spinal injury (141) or stroke (319), its use as a general analgesic is limited because of its sedative properties and the rapid development of tolerance to its pain-relieving activity. Baclofen also exhibited antinociceptive properties in rodent models of acute pain, such as the tail-flick, acetic acid writhing, Formalin, and hot-plate tests (13,273). Moreover, baclofen showed antinociceptive and antiallodynic actions in chronic pain models in rats (84,344).…”

Section: Nociceptionmentioning

confidence: 99%

Molecular Structure and Physiological Functions of GABA_BReceptors

Bettler

Kaupmann

Mosbacher

et al. 2004

Physiological Reviews

794

720

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GABAB receptors are broadly expressed in the nervous system and have been implicated in a wide variety of neurological and psychiatric disorders. The cloning of the first GABAB receptor cDNAs in 1997 revived interest in these receptors and their potential as therapeutic targets. With the availability of molecular tools, rapid progress was made in our understanding of the GABAB system. This led to the surprising discovery that GABAB receptors need to assemble from distinct subunits to function and provided exciting new insights into the structure of G protein-coupled receptors (GPCRs) in general. As a consequence of this discovery, it is now widely accepted that GPCRs can exist as heterodimers. The cloning of GABAB receptors allowed some important questions in the field to be answered. It is now clear that molecular studies do not support the existence of pharmacologically distinct GABAB receptors, as predicted by work on native receptors. Advances were also made in clarifying the relationship between GABAB receptors and the receptors for γ-hydroxybutyrate, an emerging drug of abuse. There are now the first indications linking GABAB receptor polymorphisms to epilepsy. Significantly, the cloning of GABAB receptors enabled identification of the first allosteric GABAB receptor compounds, which is expected to broaden the spectrum of therapeutic applications. Here we review current concepts on the molecular composition and function of GABAB receptors and discuss ongoing drug-discovery efforts.

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Section: Nociceptionmentioning

confidence: 99%

Molecular Structure and Physiological Functions of GABA_BReceptors

Bettler

Kaupmann

Mosbacher

et al. 2004

Physiological Reviews

794

720

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“…Animal studies indicate that baclofen has analgesic properties when injected into the spine (118,119), and, in humans, it has shown efficacy, especially in patients with central pain associated with spinal cord injury (120)(121)(122), but showing lack of efficacy in complex regional pain syndrome (123). An animal study demonstrated that intrathecal baclofen reduced only the Phase-2 pain behavior after formalin injection, suggesting that the drug blocks noxious stimulus-induced spinal sensitization (124), but also modulating the effects of neuropathic pain in a nerve injury animal model (125). PACC recommendations (72) proposed with evidence Level II-2 as intrathecal medication for use to treat spasticity, also, with evidence Level II-3 recommend as an adjuvant to treat pain in Line 4.…”

Section: Baclofenmentioning

confidence: 99%

Intrathecal Drug Delivery: Advances and Applications in the Management of Chronic Pain Patient

et al. 2022

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Advances in our understanding of the biology of spinal systems in organizing and defining the content of exteroceptive information upon which higher centers define the state of the organism and its role in the regulation of somatic and automatic output, defining the motor response of the organism, along with the unique biology and spatial organization of this space, have resulted in an increased focus on therapeutics targeted at this extracranial neuraxial space. Intrathecal (IT) drug delivery systems (IDDS) are well-established as an effective therapeutic approach to patients with chronic non-malignant or malignant pain and as a tool for management of patients with severe spasticity and to deliver therapeutics that address a myriad of spinal pathologies. The risk to benefit ratio of IDD makes it a useful interventional approach. While not without risks, this approach has a significant therapeutic safety margin when employed using drugs with a validated safety profile and by skilled practioners. The present review addresses current advances in our understanding of the biology and dynamics of the intrathecal space, therapeutic platforms, novel therapeutics, delivery technology, issues of safety and rational implementation of its therapy, with a particular emphasis upon the management of pain.

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“…Another study utilizing a similar rat formalin model also showed a substantial suppression of phase-2 behaviors. 24 Yaksh and Reddy, 25 using a primate shock-titration model of antinociception, showed that intrathecal baclofen produced significant analgesia for 14 to 18 hours. No cross-tolerance was observed between baclofen, morphine, and clonidine.…”

Section: Animal Studiesmentioning

confidence: 99%

“…They found that coadministration of ineffective doses of morphine and baclofen produced increased TF latency and CD threshold. Przesmycki et al 24 reported that intrathecal coadministration of baclofen and clonidine produced a synergistic effect on inhibition of phase 2 of the formalin test in rats.…”

Section: Animal Studiesmentioning

confidence: 99%

Intrathecal baclofen in pain management

Slonimski

Abram

Zuniga

2004

Regional Anesthesia and Pain Medicine

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Baclofen is a GABA(B) agonist that is administered spinally via an implanted drug delivery device to treat spasticity. It has been shown to have powerful antinociceptive effects in experimental animal models at doses that produce little or no motor-blocking effects but has rarely been used as a spinal analgesic agent in patients without spasticity. Several studies have indicated that intrathecal baclofen provides relief of central pain in patients with spasticity. To date, only 3 studies have shown it to be effective in patients with peripheral nociceptive or neuropathic pain mechanisms. Combinations of baclofen and morphine or clonidine are more effective than each drug alone in clinical as well as animal studies.

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An isobolographic analysis of drug interaction between intrathecal clonidine and baclofen in the formalin test in rats

Cited by 18 publications

References 42 publications

Molecular Structure and Physiological Functions of GABA_BReceptors

Molecular Structure and Physiological Functions of GABA_BReceptors

Intrathecal Drug Delivery: Advances and Applications in the Management of Chronic Pain Patient

Intrathecal baclofen in pain management

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An isobolographic analysis of drug interaction between intrathecal clonidine and baclofen in the formalin test in rats

Cited by 18 publications

References 42 publications

Molecular Structure and Physiological Functions of GABABReceptors

Molecular Structure and Physiological Functions of GABABReceptors

Intrathecal Drug Delivery: Advances and Applications in the Management of Chronic Pain Patient

Intrathecal baclofen in pain management

Contact Info

Product

Resources

About

Molecular Structure and Physiological Functions of GABA_BReceptors

Molecular Structure and Physiological Functions of GABA_BReceptors