Alpha(α) 2-Adrenergic Agonists in Pain Treatment
Alpha(α) 2-Agonists; α2c-adrenoceptor agonists; α2-receptor agonists; α2-adrenergic agonists; Alpha(α) 2-Adrenergic Receptor Agonists; α-agonists
Alpha2-adrenergic agonists are drugs that mediate their analgesic (antinociceptive) effects by acting on α2-adrenoceptors (α2A, α2B, α2C) in the peripheral and central nervous system.
Indications and Patients
Alpha2-adrenoceptor (α2AR) agonists are used for treatment of acute (intra- and post-operative) as well as chronic (neuropathic) pain states. They are effective in patients of all age groups. α2AR agonists have also been safely used in pregnancy, labour and during caesarean sections. Furthermore, there is evidence that they provide haemodynamic stability in patients with co-existing cardiovascular diseases during phases of noxious stimulation (e.g. orotracheal intubation) by attenuating the sympathetic response.
Dose and Route of Administration (Table 1)
With clonidine being the prototypical α2AR...
- 1.Bie B, Fields HL, Williams JT et al. (2003) Roles of Alpha1- and Alpha2-adrenoceptors in the Nucleus Raphe Magnus in Opioid Analgesia and Opioid Abstinence-Induced Hyperalgesia. J Neurosci 23:7950–7957Google Scholar
- 2.Dawson C, Ma D, Chow A et al. (2004) Dexmedetomidine Enhances Analgesic Action of Nitrous Oxide: Mechanisms of Action. Anesthesiology 100:894–904Google Scholar
- 3.Duflo F, Li X, Bantel C et al. (2002) Peripheral Nerve Injury Alters the Alpha2 Adrenoceptor Subtype Activated by Clonidine for Analgesia. Anesthesiology 97:636–641Google Scholar
- 4.Kawasaki Y, Kumamoto E, Furue H et al. (2003) Alpha 2 Adrenoceptor-Mediated Presynaptic Inhibition of Primary Afferent Glutamatergic Transmission in Rat Substantia Gelatinosa Neurons. Anesthesiology 98:682–689Google Scholar
- 5.Kingery WS, Agashe GS, Guo TZ et al. (2002) Isoflurane and Nociception: Spinal Alpha2A Adrenoceptors Mediate Antinociception while Supraspinal Alpha1 Adrenoceptors Mediate Pronociception. Anesthesiology 96:367–374Google Scholar
- 6.Lavand'homme PM, Eisenach JC (2003) Perioperative Administration of the Alpha2-Adrenoceptor Agonist Clonidine at the Site of Nerve Injury Reduces the Development of Mechanical Hypersensitivity and Modulates Local Cytokine Expression. Pain 105:247–254Google Scholar
- 7.Li XH, Eisenach JC (2001) a2A-Adrenoceptor Stimulation Reduces Capsaicin-Induced Glutamate Release from Spinal Cord Synaptosomes. J Pharmacol Exp Ther 299:939–944Google Scholar
- 8.Ma W, Eisenach JC (2003) Chronic Constriction Injury of Sciatic Nerve Induces the Up-Regulation of Descending Inhibitory Noradrenergic Innervation to the Lumbar Dorsal Horn of Mice. Brain Res 970:110–118Google Scholar
- 9.Nuseir K, Proudfit HK (2000) Bidirectional Modulation of Nociception by GABA Neurons in the Dorsolateral Pontine Tegmentum that Tonically Inhibit Spinally Projecting Noradrenergic A7 Neurons. Neuroscience 96:773–783Google Scholar
- 10.Pan HL, Chen SR, Eisenach JC (1999) Intrathecal Clonidine Alleviates Allodynia in Neuropathic Rats: Interaction with Spinal Muscarinic and Nicotinic Receptors. Anesthesiology 90:509–514Google Scholar
- 11.Paqueron X, Conklin D, Eisenach JC (2003) Plasticity in Action of Intrathecal Clonidine to Mechanical but not Thermal Nociception after Peripheral Nerve Injury. Anesthesiology 99:199–204Google Scholar
- 12.Sonohata M, Furue H, Katafuchi T et al. (2004) Actions of Noradrenaline on Substantia Gelatinosa Neurones in the Rat Spinal Cord Revealed by In Vivo Patch Recording. J Physiol 555:515–526Google Scholar
- 13.Stone LS, Macmillan L, Kitto KF et al. (1997) The α2a-adrenergic Receptor Subtype Mediates Spinal Analgesia Evoked by α2 Agonists and is Necessary for Spinal Adrenergic/Opioid Synergy. J Neurosci 17:7157–7165Google Scholar
- 14.Stone LS, Broberger C, Vulchanova L et al. (1998) Differential Distribution of Alpha2A and Slpha2C Adrenergic Receptor Immunoreactivity in the Rat Spinal Cord. J Neurosci 18:5928–5937Google Scholar
- 15.Stone LS, Vulchanova L, Riedl MS, Wang J, Williams FG, Wilcox GL, Elde R (1999) Effects of Peripheral Nerve Injury on Alpha-2A and Alpha-2C Adrenergic Receptor Immunoreactivity in the Rat Spinal Cord. Neuroscience 93:1399–1407Google Scholar