How Pain Works and Why It Shouldn’t Be Ignored

There is an approximate definition, and it is quite easy to understand. But how pain arises, what it affects, and what consequences it may lead to is already a much more complex question, and one that has not yet been fully studied.
Regardless of the cause, pain begins to exist as an independent phenomenon that requires separate attention from the physician. That is why more and more studies are being devoted to pain as a distinct pathological process, along with the search for reliable methods of its treatment.

Pain is defined by the International Association for the Study of Pain (IASP) as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

Researchers divide pain into acute and chronic. These types of pain differ greatly in both their mechanisms and consequences. Therefore, treatment approaches also differ.

Acute pain is a pain syndrome that develops in response to acute tissue damage. It is a protective, adaptive mechanism that warns of further injury and possible serious or even fatal consequences. Acute pain syndrome is defined as a rapidly developing response to direct injury, whether mechanical, thermal, or chemical.

Chronic pain syndrome is a long-term process associated with secondary damage to tissues and nerve endings. Another important difference lies in the localization of pain. The source of acute pain can usually be precisely localized, for example, a fractured limb. In chronic pain, precise localization is not possible. In acute pain syndrome, the pain disappears as the tissue heals and the cause is eliminated. In chronic pain, however, the underlying cause can most often not be eliminated.

In many cases, we can prevent the development of chronic pain syndrome if pain is well controlled during the acute phase. According to some studies in medicine, a significant number of postoperative patients experience chronic pain.

CHRONIC PAIN, IN TURN, CAN BE CHARACTERIZED AS:

• inflammatory pain – caused by the prolonged action of inflammatory mediators on nerve endings in the presence of tissue injury or tissue inflammation. For example, pain associated with pancreatitis.
• neuropathic pain – arising from injury to the nervous system, such as brain tumors, intervertebral disc disease, surgical excision of major nerves, and so on.

If we are talking about the development of acute pain, it is followed by an acute motor response – withdrawal of the limb, jumping away, biting – in other words, a reaction aimed at protecting the body from the obvious source of pain. If chronic pain develops, no visible motor response will occur. First, this is because the speed of impulse transmission in chronic pain is lower. Second, because in chronic pain the source of pain itself is not clearly localized, the body has no real way to defend itself against it. Usually, when chronic pain syndrome develops, the symptoms are very subtle; sometimes a veterinarian may not even recognize them during an examination because of the production, in response to stress, of endogenous cannabinoids and morphine-like substances that mask pain.

At the tissue-damage stage of pain formation, inflammatory mediators play a major role – histamine, potassium, bradykinin, leukotrienes, prostaglandins, cytokines, and serotonin. These factors are referred to as the "inflammatory soup" and cause peripheral sensitization, meaning that they affect peripheral nerve fibers, stimulate their endings, and generate a pain impulse.

To relieve pain, we must therefore use medications and techniques that reduce the severity of the primary injury. In the synapses of the dorsal horns of the spinal cord, the receptors most important for the development of acute pain syndrome are NMDA and AMPA receptors, potassium channels, and the excitatory mediator glutamate.

In the development of pathological synaptic changes, an important role is played by the large amount of glutamate, due to continuous excitation of nerve fibers from the injured tissue area, as well as NMDA receptors, magnesium channels, protein kinase C, nitric oxide, calcium in the synaptic cleft, and substance P.

In the case of prolonged stimulation of the synapse and continuous release of large amounts of glutamate into the synaptic cleft, the magnesium block of the NMDA receptor remains permanently open, allowing large amounts of calcium to enter from the synaptic cleft. This calcium acts on protein kinase C and triggers the formation of large amounts of nitric oxide, which closes potassium channels. Since opioid analgesics exert their effect through these channels, they are not effective in the treatment of chronic pain. Nitric oxide also promotes the release of large amounts of substance P, which interacts with the genetic structure of the synapse and causes irreversible morphological changes. That is why chronic pain syndrome is considered a separate disease.

The modern approach to pain treatment is based on the principle of multimodal analgesia. It involves using techniques and medications that interrupt the nociceptive pathway at two or more stages, or that act at one stage but on two or more different receptors.