Chronic non-cancer pain
If the cause of increased peripheral impulses persists, the phenomenon of increased pain also occurs in the central nervous system, which also supports pain. At the same time, the differences between “inflammatory” and neuropathic pain exist and consist in the fact that after suppression of inflammation the pain disappears and neuropathic pain can remain even if the cause is eliminated (for example, causalgia).
The prolonged course of rheumatic diseases leads to the fact that chronic pain gradually loses its protective function inherent in physiological pain. Pain that has a pathogenic effect that causes maladaptation is called pathological pain . The biological significance of pathological pain differs from the physiological mechanisms of implementation and clinical – behavioral reactions. Pathological pain loses its signal value and activating effect on the mechanisms of algogenic factor elimination. It becomes a pathogenic factor, disrupting the adaptive capacity of the body, causing disorders of the central nervous system, microcirculation, cardiovascular system, etc. Against its background, vegetative disorders such as fatigue, sleep disorders, loss of appetite, weight loss, decreased libido and constipation occur. According to the currently recognized theory of Academician G.N. Kryzhanovsky, with chronic pain syndrome on the background of long-term nociceptive impulses, new pathological interrelations of altered neurons form from the damaged tissues – the so-called pathologically enhanced excitation generator, and pathological algic system (PAS) at the system level. The overactive state of this system is maintained due to the continued irritation of peripheral pain receptors, increased release of endogenous algogenic substances that hypersensitize nociceptors. At the same time, the nature of the pathogenic agent causing the pain syndrome is not significant: the occurrence of a generator in the dorsal horns of the spinal cord plays a decisive role. Enhanced long-term synaptic stimulation creates a steady depolarization of neurons along the entire path of pain impulses – from the peripheral focus to the central structures of the brain. For the emergence of pain syndrome, it is necessary that the higher parts of the pain sensitivity system are involved in the process. The formation of PAS occurs with the development of insufficiency of the inhibitory endogenous mechanisms of nociception. According to modern concepts, the leading role in the regulation of pain belongs to endogenous analgesic systems – opioid and non-opioid. Responsible for the development of analgesia are primarily opioid m – receptors, with which endogenous opioids (endorphins) and exogenous drugs (morphine and its analogues) interact. Non-opioid receptor – humoral systems that differ in their neurotransmitters — adrenergic, serotonergic, and GABA * —ergic (* GABA –g – aminobutyric acid) also take part in pain regulation. By pharmacological effects on these systems, their agonists can achieve a certain degree of analgesia and enhance the action of narcotic and non-narcotic analgesics.
The multilevel mechanism for the formation of chronic pain syndrome suggests a complex pathogenetic approach to its treatment. The combined effect on its various links should include: suppression of the synthesis of mediators in the inflammatory focus (in particular, prostaglandins) to limit the impulse activity of the nerve C-conductors; restriction of receipt of nociceptive impulses from the damage zone in the central nervous system and activation of the antinociceptive system.
It is known that in the mechanism of pain syndrome in rheumatic diseases an important role is played by the stimulation of local pain receptors by inflammatory mediators, especially bradykinin and prostaglandins. Not being moderators of pain, prostaglandins reduce the sensitivity threshold of nociceptors to various stimuli and, thus, take part in the formation of secondary inflammatory hyperalgesia and peripheral sensitization (increased pain). It is known that proinflammatory prostaglandins are formed in the process of arachidonic acid conversion using the enzyme cyclooxygenase – 2 (COX – 2). Thus, COX-2 is directly involved in the development of a painful stimulus. It turned out that COX-2 plays an important role not only in the induction of pain in the inflammatory focus, but also in the transmission of pain impulses to the spinal cord. It has been shown that production of COX – 2 mRNA can be induced in the spinal cord after the development of peripheral inflammation, i.e. COX-2 refers to the natural enzymes expressed in the central nervous system. In experimental arthritis, direct exposure to the lumbar spinal cord with selective COX-2 inhibitors prevented inflammatory hyperalgesia. During a peripheral inflammatory reaction in the cerebrospinal fluid, the level of prostaglandins, highly sensitive to COX – 2 inhibitors, increases. It is obvious that NSAIDs, which were previously considered peripheral analgesics, can have their effect in the central nervous system. It is appropriate to note here that, until recently, it was believed that the analgesic m – receptors, the points of application of opioids, are localized only within the CNS. Therefore, substances interacting with these receptors were referred to as centrally acting analgesics. Today it has become obvious that m – receptors can appear on the nerve endings in the inflammation foci on the periphery and act as the object of exposure to m – receptor agonists. Thus, central analgesics such as morphine can have a peripheral effect, and peripheral (NSAIDs) can have a central effect.
Suppression of inflammatory pain at an early stage of its development is carried out by algogen inactivators, primarily by inhibitors of prostaglandin synthesis. The main group of drugs used for this purpose are non-steroidal anti-inflammatory drugs (NSAIDs), the universal mechanism of action of which is cyclo-oxygenase synthesis blockade. Preparations of this series have long been successfully used in the treatment of pain of various origins. They have a different ratio of analgesic, anti-inflammatory and antipyretic properties, which allows for individual selection of the most effective and safe means. The widespread use of NSAIDs has not always revealed a satisfactory risk / benefit ratio. The incidence of side effects of NSAIDs reaches about 25%, life-threatening complications – 5%. The development of known side effects of NSAIDs, due to the mechanism of action, naturally limits their use. NSAIDs suppress moderate and severe pain, but the degree of analgesia is often insufficient. Taking into account certain shortcomings of NSAIDs, it is clear that clinicians are interested in new possibilities for reducing pain in rheumatic diseases and in using more optimal treatment regimens.
Non-opioid analgesics are the safest and most common means in the fight against pain. Historically, acetylsalicylic acid and paracetamol, used since the XIX century, are used to treat pain of mild to moderate intensity. Acetylsalicylic acid was eventually replaced by other NSAIDs, and paracetamol continues to be actively used for the treatment of osteoarthritis. As an independent tool, paracetamol is not effective enough in inflammatory diseases of the joints, but it can be given in combination with NSAIDs.
With the development of severe pain, the choice of remedies is currently limited. In addition to NSAIDs, which, with severe pain, do not always provide adequate analgesia, analgesics of central action are used, since central regulation is recognized as the most specific and reliable option for pain management. The most common analgesics of the central action are opioids, but they are used primarily for cancer pain. The possibility of their use in rheumatology remains a matter of debate. For the treatment of chronic rheumatic pains of moderate and severe intensity, medium-strength opioids in small and medium doses are used in those developed countries where life expectancy is constantly increasing, older people tend to maintain functional abilities longer and generally are more demanding about quality of life. The literature suggests that with long-term use such a traditional “soft” opioid, like codeine, in patients with rheumatic diseases has a good analgesic effect in small doses, is well tolerated, and addiction develops very rarely. At the same time, analgesia based on traditional opioids is associated with a number of side effects: nausea, vomiting, constipation, respiratory depression, sedation, and the development of drug dependence. Opioids are socially dangerous, so doctors have opposition to the use of opioids for the treatment of chronic non-oncological pain, even of considerable intensity. Opioids are not available for patients with non-oncological chronic pain syndromes, even in cases where antirheumatic therapy has exhausted its possibilities, and the patient becomes, in fact, incurable.