Methods and Findings in Experimental and Clinical Pharmacology
Vol. 25, Suppl. A, 2003
ISSN 0379-0355
Copyright 2003 Prous Science, S.A.
CCC: 0379-0355/2003
http://www.prous.com

Antidepressants and Pain

J.A. Micó

Pharmacology and Neuroscience Research Group (PAI CTS-510), Department of Neuroscience (Pharmacology and Psychiatry), University of Cádiz, Cádiz, Spain

Pain is a multidimensional process involving the physical, emotional and perceptual integration of noxious information. The emotional aspect is encoded by the limbic system and encloses the relationship between pain and mood. Chronic pain such as this constitutes chronic stress, and a large proportion of patients with chronic pain also present with clear symptoms of depression. In addition, clinical reports indicate that depressed patients who do not suffer from chronic pain exhibit alterations in their perception of pain. Thus, these two phenomena could be related.

It has been estimated that over 50% of patients suffering from chronic pain also express clinically diagnosable symptoms of depression. Given the diverse origins of chronic pain, controversy surrounds the relationship it bears to the depression with which it is often coexpressed. Five major hypotheses have been proposed: i) the antecedent hypothesis, in which depression precedes the development of chronic pain; ii) the consequence hypothesis, in which depression is a consequence of the chronic pain; iii) the scar hypothesis, in which episodes of depression occurring before the onset of chronic pain predispose the patient to a depressive episode after the onset of pain; iv) the cognitive mediation hypothesis, in which psychological factors such as poor coping strategies are considered to mediate the reciprocal interactions between chronic pain and depression; and v) the independent hypothesis, in which depression and chronic pain are considered to share some common pathogenetic mechanisms but remain distinct diseases without causal interaction (1).

Several clinical studies have suggested that pharmacotherapies used to treat depression may also be effective analgesics in chronic pain sufferers. Detailed meta-analyses of multiple antidepressant trial studies indicate that antidepressants are associated with pain relief that is over 74% more effective than placebo alone in chronic pain patients. Some studies utilizing only nondepressed patients suffering from chronic neuropathic pain of nerve injury, degeneration, or postherpetic neuralgic origins, demonstrated 50% pain relief in response to antidepressants. Meta-analyses designed to control for 'masked' depression, have also demonstrated that antidepressants act in chronic pain patients through an analgesic effect rather than through an effect to improve undiagnosed depression. Although the analgesic effect of antidepressants is to some extent independent of their antidepressant properties, clinical studies have shown that mixed inhibitors of serotonin and noradrenaline reuptake have greater analgesic potency than serotonin selective drugs (2). In this sense, classical pain targets may prove useful in the generation of novel antidepressants (3).

Regarding the possible mechanisms of action implicated in the analgesic effect of the antidepressants, several hypothesis have been formulated. However, it seems clear that an enhancement of the activity of the endogenous inhibitory system regulated by opioids, serotonin and noradrenaline are directly or indirectly implicated (4-7).

ACKNOWLEDGMENTS

Supported by FIS 01/1055 and Plan Andaluz de Investigación (PAI-510).

REFERENCES

1. Blackburn-Munro, G., Blackburn-Munro, R.E. Chronic pain, chronic stress and depression: Coincidence or consequence? J Neuroendocrinol 2001, 13: 1009-23.

2. Rojas-Corrales, M.O., Casas, J., Moreno-Brea, R., Gibert-Rahola, J. Micó, J.A. Antinociceptive effects of tricyclic antidepressants and their noradrenergic metabolites. Eur Neuropsychopharmacol 2003 (In press).

3. Briley, M. New hope in the treatment of painful symptoms in depression. Curr Opin Investig Drugs 2003, 4: 42-5.

4. Valverde, O., Micó, J.A., Maldonado, R., Mellado, M.L., Gibert-Rahola, J. Participation of opioid and monoaminergic mechanisms on the antinociceptive effect induced by tricyclic antidepressants in two behavioral pain test in mice. Prog Neuropsychopharmacol Biol Psychiatry 1994, 18: 1073-92.

5. Micó, J.A., Gibert-Rahola, J., Casas, J., Rojas, O., Serrano, M.I., Serrano, J.S. Implication of b 1- and b 2-adrenergic receptors in the antinociceptive effect of tricyclic antidepressants. Eur Neuropsychopharmacol 1997, 7: 139-45.

6. Gray, A.M., Spencer, R.D., Sewell, R.D. The involvement of the opioidergic system in the antinociceptive mechanism of action of antidepressant compounds. Br J Pharmacol 1998, 124: 669-74.

7. Eschalier, A., Ardid, D., Coudore, F. Pharmacological studies of the analgesic effect of antidepressants. Clin Neuropharmacol 1992, 15: 373-4A.

Methods and Findings in Experimental and Clinical Pharmacology Vol. 25, Suppl. A, 2003
ISSN 0379-0355 Copyright 2003 Prous Science, S.A. CCC: 0379-0355/2003 http://www.prous.com