Trends in Pharmacological Sciences
Antidepressants and pain
Section snippets
Why use an antidepressant to relieve pain?*
‘Why do I have to take an antidepressant to relieve pain if I am not depressed?’ This question could be asked of a physician by a patient suffering from pain when prescribed an antidepressant as an analgesic. This is a reasonable question from the patient's perspective, and the physician should answer that the antidepressant is prescribed for its analgesic action rather than its antidepressant action. The patient's next questions might be: ‘are antidepressants pain killers?’ and ‘how is that
Tricyclic antidepressants versus selective amine-reuptake inhibitors and new dual antidepressants
Just as there is virtually an agreement that neuropathic pain is most responsive to the analgesic action of antidepressants [10], a consensus also exists that the well-known tricyclic antidepressants have the greatest analgesic efficacy 8, 9 (Table 1). Among these, particular mention should go to amitriptyline, the gold standard of analgesic antidepressants. This does not mean that other tricyclic antidepressants are less effective but that most available clinical evidence has been obtained for
Mechanism of the analgesic action of antidepressants
Most information regarding the mechanism of the analgesic action of antidepressants has been obtained in animals (rats and mice). It should be noted that the results of research into the antinociceptive action of antidepressants using acute pain tests in which different noxious stimuli (thermal, chemical, mechanical or electric) are applied cannot be extrapolated to human clinical pain [16]. In fact, antidepressants are never used to treat acute pain in humans, except for experimental research.
Impact of antidepressants on pain as a physical symptom of depression
Pain and depression are often linked, and several studies have indicated that pain and depression share common neurochemical mechanisms 26, 27. Clinical depression is common in patients with persistent chronic pain: 30–54% [28]. Conversely, pain is among the most common physical symptoms in patients with depression, and a common complaint reported to specialists [29]. Relapses into a depressive state are more common in such patients and make total symptom remission difficult, closing a vicious
Concluding remarks and future perspectives
Antidepressants have become, in their own right, common drugs for the treatment of chronic, mainly neuropathic, pain, even though their efficacy is limited. Research in this field has evolved substantially in recent years but there are still many issues to be elucidated in both preclinical and clinical research. From a clinical viewpoint, consistent criteria are required for selection of the type of antidepressant to be used, in addition to the dosage, depending on symptoms, pain type and
Acknowledgements
This study was supported by Fondo de Investigación Sanitaria (PI031430), Ministère Français de l'Enseignement Supérieur et de la Recherche, INSERM and Institut Paul Hamel.
References (73)
Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment
Eur. J. Pain
(2006)The burden of neuropathic pain: results from a cross-sectional survey
Eur. J. Pain
(2006)Duloxetine vs placebo in patients with painful diabetic neuropathy
Pain
(2005)Algorithm for neuropathic pain treatment: an evidence based proposal
Pain
(2005)Leading the charge – pioneering treatments in the fight against neuropathic pain
Trends Pharmacol. Sci.
(2003)Treatment response in antidepressant-naive postherpetic neuralgia patients: double-blind, randomized trial
J. Pain
(2005)Evaluation of reboxetine, a noradrenergic antidepressant, for the treatment of fibromyalgia and chronic low back pain
Psychosomatics
(2005)Pain-like behaviours in animals – how human are they?
Trends Pharmacol. Sci.
(2004)- et al.
Attenuation of negative pain affect produced by unilateral spinal nerve injury in the rat following anterior cingulate cortex activation
Neuroscience
(2005) Involvement of bulbospinal pathways in the antinociceptive effect of clomipramine in the rat
Brain Res.
(1995)
Fluoxetine attenuates thermal hyperalgesia through 5-HT1/2 receptors in streptozotocin-induced diabetic mice
Eur. J. Pharmacol.
Blockade of supraspinal 5-HT1A receptors potentiates the inhibitory effect of venlafaxine on wind-up activity in mononeuropathic rats
Brain Res.
Descending control of pain
Prog. Neurobiol.
Peripheral antinociceptive action of amitriptyline in the rat formalin test: involvement of adenosine
Pain
Caffeine blockade of the thermal antihyperalgesic effect of acute amitriptyline in a rat model of neuropathic pain
Eur. J. Pharmacol.
Bad news from the brain: descending 5-HT pathways that control spinal pain processing
Trends Pharmacol. Sci.
Spinal 5-HT1A receptors differentially influence nociceptive processing according to the nature of the noxious stimulus in rats: effect of WAY-100635 on the antinociceptive activities of paracetamol, venlafaxine and 5-HT
Pain
Intracerebroventricular injection of trazodone produces 5-HT receptor subtype mediated anti-nociception at the supraspinal and spinal levels
Eur. Neuropsychopharmacol.
Antinociception induced by amitriptyline and imipramine is mediated by α2A-adrenoceptors
Jpn. J. Pharmacol.
Do α2-adrenoceptors play an integral role in the antinociceptive mechanism of action of antidepressant compounds?
Eur. J. Pharmacol.
Loss of amitriptyline analgesia in α2A-adrenoceptor deficient mice
Eur. J. Pharmacol.
Spinal noradrenaline transporter inhibition by reboxetine and Xen2174 reduces tactile hypersensitivity after surgery in rats
Pain
The antinociceptive effect of moclobemide in mice is mediated by noradrenergic pathways
Neurosci. Lett.
Implication of β1- and β2-adrenergic receptors in the antinociceptive effect of tricyclic antidepressants
Eur. Neuropsychopharmacol.
Characterization of the analgesic properties of nomifensine in rats
Pharmacol. Biochem. Behav.
Effects of tricyclic antidepressants on mechanosensitive pelvic nerve afferent fibers innervating the rat colon
Pain
Opioid receptors and neuropeptides in the CNS in rats treated chronically with amoxapine or amitriptyline
Neuropharmacology
The antinociceptive effect of venlafaxine in mice is mediated through opioid and adrenergic mechanisms
Neurosci. Lett.
Tricyclic antidepressants as long-acting local anesthetics
Pain
Involvement of potassium channels in amitriptyline and clomipramine analgesia
Neuropharmacology
Amitriptyline enhances extracellular tissue levels of adenosine in the rat hindpaw and inhibits adenosine uptake
Eur. J. Pharmacol.
Reduction of NMDA-induced behaviour after acute and chronic administration of desipramine in mice
Neuropharmacology
Relationship between the antinociceptive response to desipramine and changes in GABAB receptor function and subunit expression in the dorsal horn of the rat spinal cord
Biochem. Pharmacol.
Amitriptyline prevents thermal hyperalgesia and modifications in rat spinal cord GABAB receptor expression and function in an animal model of neuropathic pain
Biochem. Pharmacol.
GABAB receptor function and subunit expression in the rat spinal cord as indicators of stress and the antinociceptive response to antidepressants
Brain Res.
Imipramine inhibits intrathecal substance P-induced behavior and blocks spinal cord substance P receptors in mice
Brain Res.
Cited by (355)
Beyond depression, antidepressants to treat chronic pain
2022, Annales Medico-PsychologiquesPharmacologic Treatment for Temporomandibular and Temporomandibular Joint Disorders
2022, Oral and Maxillofacial Surgery Clinics of North AmericaPharmacology of the Equine Foot: Medical Pain Management for Laminitis
2021, Veterinary Clinics of North America - Equine PracticeSynergistic interaction between amitriptyline and paracetamol in persistent and neuropathic pain models: An isobolografic analysis
2021, Neurochemistry InternationalCitation Excerpt :Amitriptyline is a sodium channels blocker, which gives membrane stabilizing properties to suppress the underlying ectopic neural discharges in neuropathic pain (Wang et al., 2004). Remarkably, this compound reduces several inflammatory biomarkers and immune parameters (Micó et al., 2006; Sadeghi et al., 2011). These facts suggest the pharmacodynamic rationale of the amitriptyline/paracetamol fixed-ratio combination given that different peripheral and central therapeutic targets on the nociceptive pathway could be attacked and also result in reduced adverse effects.