What is pain?
Mechanical and ischemic pain that develops within the framework of nociceptive pain also requires local therapy of the source of pain with the appointment of symptomatic treatment and, possibly, NSAIDs.
Neuropathic pain – in addition to drug therapy for the causes of pain (for example, the use of adequate doses of antiviral drugs for post herpetic neuralgia), a local effect on the source of pain is necessary (for example, a study of the level of compression in tunnelling neuropathy, radiculopathy, the use of local types of treatment: treatment blocks, perineal blockades, epidural and foramen blockages, muscle blocks during nerve compression in the muscle-tendon tunnel), as well as the appointment of drugs from the antico groups nvulsant and antidepressants, acting, in addition to nociceptive structures (perceiving and transmitting pain), on ant nociceptive structures (suppressing pain).
Therapy of dysfunctional pain can also include the appointment of anticonvulsants and antidepressants, but, in addition, must necessarily be carried out with the participation of specialists from related specialties, specialists responsible for the area of pain (otorhinolaryngology, orthodontist with facial pain, for example), and a psychiatrist whose participation is necessary to evaluate affective reactions to chronic pain.
The “golden” period of studying pain syndromes began in the second half of the 20th century, which is connected both with the development of the principles of evidence and evidence-based medicine, and with the beginning of the formation of a modern understanding of the rules of organization and adequate design of clinical studies.
Currently, studies on painkillers are being conducted to obtain data on their efficacy and safety, as regards relatively new drugs, and a comparison of their effectiveness with existing “gold standards”. If we consider the frequency of the request of RCTs (randomized clinical trials) for the use of analgesics from our website, maximum results will be obtained in the NSAID class. And the frequency of occurrence of such data is only growing. This is connected not so much with the discovery of fundamentally new drugs, but with the creation of all the new “copies of drugs” – generics containing the same chemical as the main active ingredient, the so-called international non-proprietary name (INN). The Internet is replete with messages, the essence of which boils down to finding a cheaper analogue, but at the same time they forget that often not only the INN determines the effect of the drug, but the mechanism of its processing, the pharmacokinetics and pharmacodynamics of the drug, but the data on the generic bioequivalence to the original drug trust in the generic, and this information is not always available.
The history of the creation of drugs from the class of NSAIDs begins with the XVII century, with the extensive use of quinine, which has anti-inflammatory and analgesic properties. In 1763, Edward Stone investigated the effectiveness of willow bark extract as an alternative to quinine. And a hundred years later, willow bark extract was actively used as an anesthetic. From 1824–1829, a large number of works were reported, informing about the first isolation of the substance salicylate from the willow bark, which, in fact, was the birth of the NSAID class. Since 1860, the Kolbe-Schmitt reaction has become the main method for the synthesis of salicylic acid. The first synthetic NSAID was antipyrine (phenazone), which appeared 14 years earlier than its more well-known fellow – aspirin – and held on the pharmacological market to date. Then there was the invention of amidopyrine (pyramidon) in 1893, which became the “gold standard” and entered folk folklore, films and performances by satirists.
Further development of the pharmacological market of anaesthetics proceeded by leaps and bounds
Encountering only those or other complications inherent in each class of drugs. Thus, myelotoxicity blocked the development of pyrazolone derivatives, the use of metamizole sodium was limited due to possible hematological problems, the drug phenibutazone, which arose in 1949, also received a restriction of use because of myelotoxicity, and for the first time systematic ulcerogenic complications were noted. Phenacetin, produced in 1878, as it turned out much later, had a high neurotoxicity and increased the risk of developing cancer.
Thus, by the 1970s – 1980s, the most significant complication of the next “gold standard,” acetylsalicylic acid, was LCD complications. It is for the severity of ulcerogenity compared new NSAIDs with existing. The next significant step was the discovery of two isoforms of the enzyme cyclooxygenase and the creation of coxibs, selective COX-2 inhibitors. The emergence of this class of NSAIDs was controlled by clinical trials SUCCESS-1, then there were extensive studies of MEDAL, CONDOR, APPROVe, VIGOR, during which revealed complications associated with the risk of thrombotic complications, later called “Coxib crisis”. Currently, the safety assessment of NSAIDs and studies of drugs available on the market confirm the relative safety of all drugs, with reasonable restrictions on their use due to the possible risks of adverse reactions.