Revue des thérapeutiques pharmacologiques actuelles de la douleur
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Les progrès récents dans le domaine de la recherche ont transformé l’approche et la compréhension de la physiopathologie de la douleur. A chaque étape de la douleur, une multitude d’effecteurs ont été découverts interagissant les uns avec les autres, pouvant inhiber ou au contraire sensibiliser cette sensation. Ces multiples composantes font que la prise en charge de la douleur entraîne fréquemment le recours à des modalités thérapeutiques variées.
L’approche pharmacologique est néanmoins la méthode de traitement la plus habituelle: on fait appel pour cela aux morphiniques, aux antalgiques non-morphiniques et/ou aux adjuvants. Il est souvent illusoire d’essayer d’obtenir un résultat par un traitement unique et le succès vient souvent de l’association de différentes substances pharmacologiques. Le praticien ne doit pas négliger non plus les approches psychologiques, la kinésithérapie, les thérapeutiques plus agressives (anesthésiques ou neurochirurgicales).
La recherche aujourd’hui a pour objectif la mise au point de l’antalgique “idéal” pouvant agir sur plusieurs cibles en bloquant spécifiquement les substances algogènes ou sensibilisatrices.
Ce développement se heurte à la multiplicité des cibles et des interactions. En pratique clinique, les progrès sont venus ces dernières années d’une meilleure connaissance de produits “anciens” comme la morphine. De nouvelles voies d’administration apparaissent, mais aussi des molécules originales comme par exemple le tramadol, qui a la particularité de présenter une double composante, opioïde et non-opioïde.
A Review of Current Pharmacological Treatment of Pain
Pain is the main reason prompting patients to consult their physicians. In acute conditions, pain has a very particular significance as a warning sign, enabling the physician to attempt a diagnosis. Nevertheless, its detrimental effect upon the individual (even in the case of acute pain) and its cost to society are now widely acknowledged. There can be no doubt about the physical component of pain, but the psychological and social aspects should not be ignored, particularly in the case of chronic pain. There is no single therapeutic approach to pain and, more often than not, successful treatment comprises a combination of several. Pharmacological treatments are undeniably the most common approach. In clinical practice, recent advances have been based upon an improved understanding of ‘old’ substances such as morphine and, at the same time, research continues in the hope of finding the ‘ideal’ analgesic — effective in most situations but without adverse effects: this appears to be a somewhat Utopian aim at present, considering the number of different causes of pain.
An improved understanding of the physiological mechanisms of pain has led, within the field of clinical practice, to several methods of differentiating pain. These depend on whether or not pain responds to morphine, or on the type of pain: pain due to an excess of nociception, pain resulting from deafferentation (caused by damage to nerve pathways) in the central or peripheral nervous system and psychogenic (idiopathic) pain. Likewise, there are several different ways of classifying analgesic treatments: according to the intensity of pain, as with use of the WHO ladder (which is based on the notion of steps) for the treatment of cancer pain; according to the presumed physiopathological mechanism and, in particular, the response to morphine; and according to the presumed central or peripheral mechanism of the drugs. In reality, peripherally acting drugs can also have a central mechanism of action, just as drugs known to have a central mechanism of action can also have peripheral activity.
As a result, several therapeutic classes have been identified. Firstly NSAIDs, which act by inhibiting the enzymes that synthesise prostaglandins, cyclo-oxygenases (COX-1, COX-2), but which also act upon lipo-oxygenases. Their efficacy is interesting, although somewhat limited by both their ceiling effect and the frequent adverse gastrointestinal reactions they produce. Specific inhibitors of COX-2 could well reduce the risk of adverse effects.
Opioids constitute the first-line treatment for pain, particularly severe pain. There are several classifications for these drugs. Firstly, weak opioids (such as codeine) and strong opioids (such as morphine) are differentiated. Secondly, a distinction is made between pure agonists (such as morphine), partial agonists (such as buprenorphine), agonist-antagonists (such as nalbuphine) and antagonists (such as naloxone). Finally, agents are distinguished on the basis of their chemical structure (synthetic, semi-synthetic or natural derivatives).
These molecules act upon different receptors (μ, δ, κ, σ) and, although peripheral mechanisms have been described, their activity occurs mainly at spinal and supraspinal levels. They provide a potent analgesic effect but are also responsible for various adverse effects — nausea, vomiting, sedation, constipation and respiratory depression — which seriously limit their use. As long as the indication is appropriate, these drugs should not be witheld because of fear of dependence or abuse.
It has been observed that other adjuvant therapeutic approaches, generally used to treat conditions other than pain, provide pain relief in certain situations. These include corticosteroids, which are widely used in rheumatology and oncology, and antidepressants, which are frequently used to treat chronic pain, especially that with a neuropathic component. Anti-epileptics are also used, particularly for excrutiatingly violent types of pain. The long list of other substances used in the treatment of pain includes local anaesthetics, baclofen, benzodiazepines, Clonidine, capsaicin and antipsychotics.
The administration of analgesics is the most common method of providing pain relief. Nevertheless, other techniques, including psychological approaches, physiotherapy, or more aggressive methods (such as anaesthetics or neurosurgery) must not be ignored. In many cases, it is misleading to think that one single treatment will provide a satisfactory result; successful pain relief generally comes from a combination of different approaches, particularly with pharmacological treatments.
The diversity of targets and interactions is a challenge in the development of new analgesics. New routes of administration have been employed, as have innovative molecules such as tramadol. This agent is atypical in that it possesses not only an opioid effect but, since it inhibits monoamine reuptake, also a non-opioid component.
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