Open Trial of Pindolol in the Treatment of Fibromyalgia

Wood, Patrick B.; Kablinger, Anita S.; Caldito, G

doi:10.1345/aph.1g014

Cited by 33 publications

(23 citation statements)

References 23 publications

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“…Furthermore, it is known that genes that modulate ␤-adrenergic receptor-mediated signaling, such as catechol-O-methyltransferase (COMT), affect pain sensitivity in vivo (Nackley et al, 2007), and genetic variants of COMT are predictive of development of temporamandibular disorder, a generalized pain syndrome (Diatchenko et al, 2005). Also consistent with this idea, the ␤-adrenergic receptor antagonist pindolol has shown promise in a preliminary trial for fibromyalgia (Wood et al, 2005).…”

Section: Discussionmentioning

confidence: 95%

Stress Induces a Switch of Intracellular Signaling in Sensory Neurons in a Model of Generalized Pain

Khasar¹,

Burkham²,

Dina³

et al. 2008

J. Neurosci.

155

169

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Stress dramatically exacerbates pain in diseases such as fibromyalgia and rheumatoid arthritis, but the underlying mechanisms are unknown. We tested the hypothesis that stress causes generalized hyperalgesia by enhancing pronociceptive effects of immune mediators. Rats exposed to nonhabituating sound stress exhibited no change in mechanical nociceptive threshold, but showed a marked increase in hyperalgesia evoked by local injections of prostaglandin E 2 or epinephrine. This enhancement, which developed more than a week after exposure to stress, required concerted action of glucocorticoids and catecholamines at receptors located in the periphery on sensory afferents. The altered response to pronociceptive mediators involved a switch in coupling of their receptors from predominantly stimulatory to inhibitory G-proteins (G s to G i ), and for prostaglandin E 2 , emergence of novel dependence on protein kinase C. Thus, an important mechanism in generalized pain syndromes may be stress-induced coactivation of the hypothalamo-pituitary-adrenal and sympathoadrenal axes, causing a long-lasting alteration in intracellular signaling pathways, enabling normally innocuous levels of immune mediators to produce chronic hyperalgesia.

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Section: Discussionmentioning

confidence: 95%

Stress Induces a Switch of Intracellular Signaling in Sensory Neurons in a Model of Generalized Pain

Khasar¹,

Burkham²,

Dina³

et al. 2008

J. Neurosci.

155

169

View full text Add to dashboard Cite

show abstract

“…Additionally, individuals with myofacial pain conditions have higher catecholamine levels and augmented sympathetic responses to stressors (Evaskus and Laskin 1972;Perry et al 1989). As with arthritis, βAR antagonists provide significant pain relief for patients with fibromyalgia (Wood et al 2005) and TMJD (Bhalang et al 2004). …”

mentioning

confidence: 99%

Catechol- O -methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors

Nackley

Tan

Fecho

et al. 2007

Pain

252

200

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Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Our group demonstrated that human genetic variants of COMT are predictive for the development of Temporomandibular Joint Disorder (TMJD) and are associated with heightened experimental pain sensitivity (Diatchenko et al. 2005). Variants associated with heightened pain sensitivity produce lower COMT activity. Here we report the mechanisms underlying COMT-dependent pain sensitivity. To characterize the means whereby elevated catecholamine levels, resulting from reduced COMT activity, modulate heightened pain sensitivity, we administered a COMT inhibitor to rats and measured behavioral responsiveness to mechanical and thermal stimuli. We show that depressed COMT activity results in enhanced mechanical and thermal pain sensitivity. This phenomenon is completely blocked by the nonselective β-adrenergic antagonist propranolol or by the combined administration of selective β 2 -and β 3 -adrenergic antagonists, while administration of β 1 -adrenergic, α-adrenergic, or dopaminergic receptor antagonists fail to alter COMT-dependent pain sensitivity. These data provide the first direct evidence that low COMT activity leads to increased pain sensitivity via a β 2/3 -adrenergic mechanism. These findings are of considerable clinical importance, suggesting that pain conditions resulting from low COMT activity and/or elevated catecholamine levels can be treated with pharmacological agents that block both β 2 -and β 3 -adrenergic receptors. Keywords epinephrine; norepinephrine; catecholamines; allodynia; hyperalgesia; carrageenan Catecholamines and enzymatic pathways that regulate the bioavailability of catecholamines influence persistent pain. Adrenergic systems contribute to the pathogenesis of rheumatoid Corresponding Author: Andrea G Neely, Center for Neurosensory Disorders, School of Dentistry, CB 7450, University of North Carolina, Chapel Hill, NC 27599-7450, Phone: (919) 966-2953, Fax: (919) Email: andrea_nackley@dentistry.unc.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptPain. Author manuscript; available in PMC 2007 July 2. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript arthritis in animals, as denervation of sympathetic noradrenergic fibers (Levine et al. 1986a) and depletion of peripheral epinephrine (Coderre et al. 1990) attenuate arthritic responses. Additionally, chronic administration of β-adrenergic receptor (βAR) agonists produces a painful arthritis-like s...

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“…The study concluded that pregabalin monotherapy provides clinically meaningful benefit to patients with FM. (68). Despite the suggestion of relative growth hormone (GH) deficiency in FM patients and reports of improvements after the administration of GH injections, the enthusiasm for this approach has been dampened by the appearance of adverse effects, the need for frequent injections, and its high cost (69).…”

Section: Anticonvulsants/antiepileptic Drugsmentioning

confidence: 99%

Fibromyalgia syndrome: the pharmacological treatment options

Sarzi-Puttini¹,

Torta²,

Marinangeli³

et al. 2011

Reumatismo

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Open Trial of Pindolol in the Treatment of Fibromyalgia

Abstract: While the current results are encouraging, further studies are needed to determine whether pindolol might be effective in the treatment of fibromyalgia. Limitations of this study include small group size and lack of placebo control.

Cited by 33 publications

References 23 publications

Stress Induces a Switch of Intracellular Signaling in Sensory Neurons in a Model of Generalized Pain

Stress Induces a Switch of Intracellular Signaling in Sensory Neurons in a Model of Generalized Pain

Catechol- O -methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors

Fibromyalgia syndrome: the pharmacological treatment options

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