Michele Curatolo, M. D., Ph. D. Department of Anaesthesiology, Division of Pain Therapy. University Hospital of Bern, Switzerland

Introduction
Chronic musculoskeletal pain conditions represent an enormous health and social problem. This indicates the inefficacy of the current available therapies in providing resolution of pain and disability. In this paper, the therapies that are commonly offered are first briefly described. Then, based on recently gained knowledge and current research, future perspectives in the pharmacological treatment of musculoskeletal pain conditions are reviewed.

Currently Used Therapies
Non-Steroidal Anti-inflammatory Drugs (NSAIDs). NSAIDs are widely used in musculoskeletal pain conditions. The recent introduction of inhibitors of the cyclooxigenase-2 enzyme (COX-2) has improved the side-effect profile of NSAIDs. 1 However, COX-2 inhibitors are not better than non-specific COX inhibitors in relieving pain, and the quantitative effect on pain and disability is modest 1 . The long-term effects of daily use of these drugs is not yet known.

Steroids.Epidural steroids may be effective in lumbosacral radiculopathy, but are not effective in the treatment of primary musculoskeletal disorders 2 . Steroid injection into the zygapophysial joints is not effective in chronic pain after whiplash injury 3 . Intraarticular steroids may be useful in patients with painful shoulder syndrome 4 .

Myorelaxants.Myorelaxants may be effective in acute low back pain with muscle spasm 5 , but the benefits for chronic pain are unclear.

Opioids.Opioids are increasingly used for chronic non-cancer pain. Oral opioids reduce pain intensity in patients with chronic musculoskeletal pain 6 . However, pain relief is quantitatively modest and usually not associated with functional or psychological improvements 6 . To date, there is a lack of long-term, prospective, controlled, studies on the use of opioids in musculoskeletal pain.

Antidepressants.Antidepressants are more effective than placebo in relieving chronic low back pain, but the difference is quantitatively modest 7 .

Future Perspectives
Intraforaminal Steroids.Selective intraforaminal epidural injection of steroids with bupivacaine is more effective than bupivacaine alone in obviating the need for an operation in patients with lumbar radicular pain 8 . This method appears of great interest because of the possibility to inject the whole amount of the drug very close to the target. The intraforaminal injection has therefore the potential to replace the traditional epidural approach.

Antagonists of the NMDA-Receptor. Psychophysical human studies have revealed the presence of hyperalgesia in patients with chronic musculoskeletal pain, which results from alterations in the central processing of nociceptive input 9 . At present, the role of this mechanism in the determination of the pain complaints is unclear. Specific treatment of hyperalgesia associated with central hypersensitivity is the use of NMDA-receptor antagonists 10 . The clinical use of the currently available NMDA-antagonists is limited by psychogenic side-effects. The development of potent NMDA-antagonists that are better tolerated may open new perspectives in the pharmacological treatment of musculoskeletal pain.

Cannabinoids.Drugs acting at the cannabinoid receptors produce analgesia and enhance morphine-induced antinociception in the animal 11 . If these findings are confirmed in humans, cannabinoids are potentially interesting in pain management. To date, these drugs are still in the list of forbidden substances in most countries.

Local Anaesthetics.Local anaesthetics may provide complete pain relief in musculoskeletal pain arising from defined structures. Blocking nerve conduction by radiofrequency lesion is still the only scientifically validated treatment that provides complete pain relief in patients with neck pain arising from the zygapophysial joints 12 . Short-lasting effect and unselective block of all fibre populations strongly limit the usefulness of local anaesthetics in chronic pain. However, the pharmacological effects can be prolonged by encapsulating local anaesthetic into liposomes 13 or slowly biodegradable polymers 14 . C-selective sodium channel blockers are under investigations 15 . The availability for clinical practice of long-acting, C-fibre specific, local anaesthetics would enable long-lasting pain relief in selected musculoskeletal pain conditions.

Drug Combinations.As for other pain conditions, analgesics are variously combined for musculoskeletal pain. Pharmacological therapies are also combined with non-pharmacological approaches. To date, the optimal combination resulting from the different therapeutic strategies is not known. Recently, an optimisation model has been applied for the first time to a clinical investigation 16 . This model may provide a rational approach for identifying optimal combinations of therapeutic strategies.

Conclusions The currently available drugs are frequently successful in reducing the level of pain, but the effect size is modest. If complete pain relief and resolution of disability is the aim of treatment, we must admit that there is no new pharmacological therapy by which these goals can be reached. Recent developments open new perspectives in the pharmacological treatment of musculoskeletal pain that may represent important steps towards satisfactory pain management. Regrettably, the way still appears long and impervious.

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Pain in Europe III. EFIC 2000, Nice, France, September 26-29, 2000. Abstracts book, p. 134 - 135.