Types of Pain and Pain Relief
The class of painkillers is very wide, and there are many classifications of drugs used in practice. The main analgesics with an analgesic effect are paracetamol, non-steroidal anti-inflammatory drugs or drugs (NSAIDs and NSAIDs), opioids and local anesthetics.
Kinds of painkillers
The drugs with analgesic properties and used in the treatment of pain syndromes of different localization include means for relieving the pain associated with changes in the pain threshold, damage (or dysfunction) in the structures of the central and peripheral nervous system, such as flupirtine, antidepressant drugs, anticonvulsant groups. Also, drugs that do not exert an analgesic effect but which intensify the analgesic effect of other drugs are regularly used. These include muscle relaxants and antispasmodics.
A strict classification of pain medications is based on the principle of drug separation into opioid, non-opioid and combination drugs, including non-opioid and opioid drugs. The remaining drugs are referred to as the so-called adjuvant and symptomatic means, allowing to achieve the desired effect with minimal side effects and in less time. The maximum prevalence of non-opioid drugs, all of which are non-narcotic, are most often facilitated by OTC drugs in the pharmacy chain.
The peculiarity of our country, in contrast to the countries of Europe and America, is the smaller spread of the use of paracetamol drugs and the unreasonably high use of antispasmodics. Opioid drugs, most of which are related to narcotic drugs, are much less common, which is associated with the significant complexity of the procedure for prescribing and recording the turnover of narcotic drugs. However, despite the fact that in our country the registration of narcotic drugs makes their appointment difficult, in European and American countries the appointment procedure is simpler, while the account and expert assessment of the patient's social and psychological characteristics fall on the shoulders of the prescribing physician, including control of the drug level in blood plasma, registration of prescribed drugs, counting used ampoules and so on. A special subclass of drugs from opioid drugs are potent drugs that do not possess narcotic properties because of their low narcogenic potential (low ability to cause psychological dependence), which is easier to account for, which allows them to be used more widely.
Acute and chronic pain
Pain is just a signal that informs us about the presence of current or possible tissue damage. Depending on the type and type of pain, temporal characteristics, the pain mechanism of the so-called nociceptive transmission varies somewhat, which also changes the pharmacological types of drugs prescribed for the therapy of a particular pain syndrome.
If you dwell on some approaches to understanding pain as such, you need to highlight the concepts of acute and chronic pain and the mechanisms of their formation. Acute pain is physiological: it is a signal of danger, reporting local damage. If the destruction of tissue is not too great, then the development of pain is temporary. The mechanism of its formation is simple: the activation of peripheral pain receptors (or nociceptors) in the area of damage develops, is transmitted along nerves to the posterior horns of the spinal cord, switches to the ascending pathways of the spinal cord and activates the structures of the central nervous system. The reflex response to the painful afferent (upward impulse) is a muscle reaction (the investigation of the relationship of which is evaluated by the nociceptive flexor reflex). As a result, a person involuntarily removes the damaged area from the danger zone, where damage is inflicted.
Chronic pain is pain that lasts longer than the period of normal healing, often non-obvious damage. It is chronic pain that is currently a significant social, economic and, of course, medical problem.
In this case, the key role is played by the mechanisms of the formation of a particular pathophysiological type of pain. This is the emergence or activation of the so-called inflammatory cascade, passing through the enzyme cyclooxygenase (COX), which has two isoforms (COX-1 and COX-2), influenced by both the analgesic effect of NSAIDs that block COX and the development of side effects reactions on the part of the gastrointestinal tract (risks of exacerbations of peptic ulcer or gastritis, mainly associated with isoform 1), as well as the possibility of increasing the risk of thrombosis, mainly associated with the isoform 2.
Changes in chronic pain occur at the level of the central nervous system: the super-strong and long excitation of peripheral nociceptors leads to sensitization of the central no-genic structures, which afterwards even react to a weak signal with pronounced and persistent excitation. Central sensitization is mediated by mediators of inflammation: with severe pain - such as tumor necrosis factor ? (TNF?), interleukin (IL) 1 and 6, and PGE2. There is a change in the properties of neuronal membranes; In this process, great importance is attached to the glutamate receptors (NMDA - N-methyl-D-aspartate receptors) and the so-called slow calcium channels.
Local inflammation, peripheral and central sensitization are normal adaptive mechanisms necessary to repair lesions. At the same time, it is these changes that are triggered or changed during the formation of chronic pain.
Nociceptive, neuropathic and dysfunctional pain
Another important classification, the use of which in clinical practice makes it possible to shorten the patient's recovery period, is the separation of pain by mechanisms of damage (the so-called pathophysiological classification) into nociceptive, neuropathic and dysfunctional.
Nociceptive pain is usually clearly localized, because it is caused by damage to specific structures. Nociceptive pain is associated with movement and activity, pain can increase or, on the contrary, decrease significantly and even disappear when moving and changing the physical state, with a change in the position of the body. Nociceptive pain can be divided into inflammatory, mechanical and ischemic.
Neuropathic pain is indeterminate, it is difficult for patients to specify its exact localization. It is characterized by considerable intensity and bright emotional coloring. Patients give her different characteristics, describe them with descriptors: "burning", "cutting", "cold", "like electric shock", "mute", "reducing". Neuropathic pain is characterized by a combination of increased excitability of the peripheral nervous system and the central nervous system and sensitivity disorders. There are phenomena of hyperalgesia (pronounced pain reaction to a slight pain stimulation), allodynia (the appearance of pain with non-spontaneous stimuli), hypo- and anesthesia, and paresthesia (sensation of crawling, itching, numbness, and so on).
Common examples of neuropathic pain are pain in diabetic polyneuropathy, postherpetic neuropathy, trigeminal neuralgia, with radiculopathy, compression-ischemic, or tunneling neuropathies (carpal tunnel syndrome).
Dysfunctional pain may resemble nociceptive, but in the absence of organic tissue damage. This type of pain is characterized by a discrepancy between the severity of the patient's suffering and the data of an objective examination. Prolonged pain or other cause leads to a decrease in inhibitory antinociceptive signals (disinhibition), which is manifested by increased excitability of painful neurons (central sensitization). Dysfunctional pain is often accompanied by symptoms characteristic of neuropathic pain, in particular hyperalgesia and allodynia.
Action painkillers
Mechanical and ischemic pain developing 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 of the causes of pain (for example, the use of adequate doses of antiviral drugs in postherpetic neuralgia), it is necessary to localize the source of pain in its presence (eg, the level of compression in tunneling neuropathy, radiculopathy, the use of local therapies: perineural blockades, epidural and foraminic blockades, muscular blockades in the compression of the nerve in the muscle-tendon tunnel), as well as the appointment of drugs from the groups of antico nuwants and antidepressants, acting in addition to nociceptive structures (perceiving and transmitting pain), to antinociceptive structures (overwhelming pain).
Dysfunctional pain therapy may also include the appointment of anticonvulsants and antidepressants, but must also be carried out with the participation of specialists in related specialties, specialists in the field of pain (otorhinolaryngologist, dentist-orthodontist in facial pains, for example) and a psychiatrist whose participation is necessary to assess affective reactions to chronic pain.
History of the study of painkillers
The "golden" period of the study of 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 the adequate design of clinical studies.
Currently, studies on painkillers are being conducted to obtain data on their efficacy and safety, as for relatively new drugs, and a comparison of efficacy with the available "gold standards". If we take into account the frequency of the RCT request (randomized clinical trials) for the use of analgesics in pubmed.com, the maximum results will be obtained in the class of NSAIDs. And the frequency of occurrence of such data is only growing. This is due not so much to the discovery of fundamentally new drugs, but to the creation of all new "copy preparations" - generics containing the same chemical substance as the main active substance, the so-called international non-proprietary name (INN). The Internet is full of messages, the essence of which is to search for a cheaper analogue, at the same time forget that often not only the INN determines the effect of the drug, but also the mechanism of its treatment, the pharmacokinetics and pharmacodynamics of the drug, but the data on the bioequivalence of the generic drug do not always inspire trust in the generic, and not always this information is available.
The history of the creation of drugs from the class of NSAIDs begins with the XVII century, with extensive use of quinine, which has anti-inflammatory and analgesic properties. In 1763 Edward Stone investigated the effectiveness of the willow bark extract as an alternative to quinine. And a hundred years later, the willow bark extract was actively used as an anesthetic. Since 1824-1829, many works have been linked, informing about the first allocation of the substance from the willow bark - salicylate, which, in fact, was the birth of the class of NSAIDs. Since 1860, the Kolbe-Schmitt reaction has become the main way to synthesize salicylic acid. The first synthetic NSAID was antipyrine (phenazone), which appeared 14 years earlier than its more famous colleague - aspirin - and stayed on the pharmacological market to date. Next was the invention of amidopyrine (pyramidone) in 1893, which became the "gold standard" and entered folk folklore, films and performances of satirists.
Further development of the pharmacological market of painkillers went by leaps and bounds, encountering only certain 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 hematologic problems, the drug phenibutazone, which appeared in 1949, also received restriction of use due to myelotoxicity, and for the first time systematic systemic ulcerogenic complications were noted. Fenacetin, produced in 1878, as it turned out later, had a high neurotoxicity and increased the risk of developing cancer.
Thus, by the 1970s and 1980s, the most significant complication of the next "gold standard" - acetylsalicylic acid - was an HC complication. It was the severity of ulcerogenicity that compared the new NSAIDs with those available. The next significant step was the discovery of two isoforms of the enzyme cyclooxygenase and the creation of coxibs - selective inhibitors of COX-2. The appearance of this class of NSAIDs was controlled by clinical studies of SUCCESS-1, followed by extensive studies of MEDAL, CONDOR, APPROVe, and VIGOR, which revealed complications associated with the risk of thrombotic complications, later called the "coxib crisis". Currently, the evaluation of the safety of NSAIDs and the research of the drugs available on the market confirm the relative safety of all drugs, subject to reasonable restrictions on their use in connection with the possible risks of adverse reactions.
The most powerful painkillers
Of the total painkillers, opioid analgesics are the strongest, while taking into account the current perception of the pain syndrome as a multidisciplinary problem, the appointment of an opioid analgesic does not always guarantee adequate therapy of the pain syndrome itself with a reflex muscle response or with myofascial syndrome (muscular-tonic syndrome), altered motor stereotype (kineziofobicheskoe disorder, defensive in fact and involved in chronic pain) and altered emotional-affective reactions.
At the same time, many studies on the effectiveness of NSAIDs have now led to an understanding of the comparable efficacy of all NSAIDs at various risks of therapy, provided that the dosage regimen and the duration of prescription are respected, depending on the pharmacokinetics and pharmacodynamics of specific drugs and their dosage forms.
Perspectives of painkillers
Despite more than a century of the use of analgesics, in the pharmacological era, studies of various new classes of drugs with analgesic activity are continuing, these are drugs acting on different pathophysiological stages of the formation of pain sensation (nociceptive system), and also drugs with activity against structures , suppressing pain transmission (antinociceptive system).
At the same time, the most important in the daily clinical practice are attempts to soften the requirements for the formulation of the nomenclature side of the prescription of opioid preparations lately. However, each innovation has a downside. With a softening of the rules for prescribing opioids, the burden of responsibility for monitoring the use, appointment, and adequate definition of the testimony will fall on the shoulders of doctors. Whether this can be perceived by practicing physicians, whether the primary care physicians will be able to observe the step-by-step treatment, determine the source and pathophysiological mechanism of pain, adequately cover all the stages of therapy, correctly explain the patient the problems of pain syndrome therapy, the timing of the development of the effect, assess the presence of psychosocial risk factors narcotic and opioid drugs and, finally, to choose an opioid analgesic, to track the correctness of its use - time will tell.
