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Chronic pain: toward new therapeutic approaches

Objective

Our aim is to analyze the mechanisms of chronic pain, based on three distinct, but overlapping objectives:
Pathophysiological mechanisms underlying various types of chronic pain.
The role of various classes of signal substances in chronic pain.
Clinical application of experimental data and meta-analysis of clinical data.

Chronic pain is a major health problem which accompanies a large number of diseases involving a broad patient population. Whatever the cause, chronic pain causes much suffering because of its severity and persistence. Furthermore, being usually associated with other chronic diseases, the presence of pain further decreases the quality of life. Finally, and possibly worst of all, a large number of chronic pain patients cannot be statisfactorily managed by currently available treatments which usually are more effective in treating pain associated with acute tissue injury, such as postoperative pain. The different responsiveness to analgesic therapy between chronic and acute pain are best illustrated by the relative ineffectiveness of opiates in treating chronic neuropathic pain. The development of currently available methods for pain management has been based on normal somatosensory functions and/or under the presence of relatively brief painful stimuli. However, based on extensive experimental studies on animals, it has recently become increasingly apparent that conditions which cause chronic pain are associated with substantial morphological, functional and pharmacological changes. Such plasticity in nervous system function may not only underly the pathophysiology of chronic pain, but may also clarify the reason for the lack of effect of traditional analgesic approaches, since their mode of action in the normal nervous system may not be useful in chronic pain states. These changes can be very remarkable, as for example transection of primary afferents results in a highly altered phenotype of chemical messengers in primary afferents. Such changes can be also very complicated as peripheral inflammation and nerve injury results in a number of diametrically opposite changes in neurotransmitter levels in primary afferents and spinal cord. Therefore, only through systematic studies of plasticity in the nervous system under various conditions known to be associated with chronic pain can we hope to gain a better understanding of the events leading to the development of pain under different pathophysiological conditions and the mechanisms accountable for various types of pain. This should then lead the way toward developing rational treatment strategies in the clinic based on different pain mechanisms.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Karolinska Institute
Address
Huddinge University Hospital
141 96 Huddinge
Sweden

Participants (7)

Institut National de la Santé et de la Recherche Médicale
France
Address
4,Avenue De L'observatoire
75270 Paris
Institut National de la Santé et de la Recherche Médicale
France
Address
2,Rue D'alesia
75014 Paris
Pathophysiology Center for the Nervous System
Italy
Address
Via Arqua 80/A
41100 Modena
Stockholms Universitet
Sweden
Address
21 A,svante Arrhenius Vag
106 91 Stockholm
The Chancellor, Master and Scholars of the University of Oxford
United Kingdom
Address
7,Churchill Hospital
OX3 7LJ Oxford
University College London
United Kingdom
Address
Gower Street
WC1E 6BT London
University of Helsinki
Finland
Address
4,Haartmaninkatu
00290 Helsinki