Pain syndrome: from pathophysiology to therapy

When pain becomes a disease in its own right and is no longer a warning function of the body, it is referred to as chronic pain syndrome. In addition to the leading symptom, this is often accompanied by other complaints such as sleep disturbances, lack of appetite or depressed mood. The psychological burden on patients is enormous, so effective therapy management is indicated.

Pain – a mad signal of the body, at least in the original sense. However, if the sensory and emotional experiences that are perceived as unpleasant occur independently of an acute event and persist, they have lost their delusional function. Then they are usually no longer a symptom of the disease, but a disease in their own right. Pain is considered chronic if it persists beyond an understandable cause and lasts longer than three or six months. The causes are usually acute injuries, diseases or incorrect posture. These include, for example, wear and tear of the musculoskeletal system, vascular diseases, neuropathic pain or tumor pain. In primary chronic pain disorder, the symptoms occur periodically, as in migraine. In addition, however, acute pain may persist. Then the pain threshold was lowered to such an extent that even external stimuli that are actually harmless are perceived as painful. In some patients, pain fibers are activated even when there is no stimulus at all. This pain memory is dependent on somatic, psychological and social factors.

Stress resistance is triggered by different mechanisms. In this context, gene polymorphisms, such as the catechol-O-methyltransferase polymorphism or the μ1-opioid receptor polymorphism, may contribute to pain sensitization. At the epigenetic level, the extent of methylation of the NR3C1 promoter gene is responsible for the expression of glucocorticoid receptors in the hippocampus.

The experience of being constantly exposed to pain without being able to control it is extremely stressful for patients psychologically. There may be a loss of zest for life, stress or even depression. Often, a protective posture is also adopted and movement is reduced, which, however, initiates a veritable vicious circle and leads to even more severe pain. Patients also gradually fall into social isolation due to depressed mood and inactivity. Over time, many of those affected are even threatened with the loss of their job or early retirement.

Complex phenomenon, multimodal therapy

In order to effectively counter these complex processes, comprehensive and modern therapy management is always multimodal. It usually consists of five pillars: medicinal, physiotherapeutic, psychotherapeutic, social and invasive. It is important for drug intervention to be on a fixed schedule, with individualized dosing, anticipation of pain, controlled dose adjustment, and active side effect management. The anticipation of pain includes the next administration of medication before the pain recurs. The aim of these measures is to achieve the greatest possible continuous pain relief or, ideally, freedom from pain.

Medicinal pain therapy is based on three levels according to the World Health Organization (WHO) pain scheme:

Stage 1: Non-opioid analgesics (Nonsteroidal anti-inflammatory drugs).
Stage 2: low-potency opioid analgesics + non-opioid analgesics.
Stage 3: high-potency opioid analgesics + non-opioid analgesics.

In pain patients without tumors, nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications. Especially for mild to moderate pain, they show a good effect. However, in elderly and/or multimorbid patients and those on co-medication, special attention should be paid to good gastrointestinal, renal, and cardiovascular tolerability in addition to rapid onset and long duration of action. In addition, there should be no significant effect on platelet aggregation. The only indications for temporary therapy with opioids are diabetic nerve damage, after shingles, osteoarthritis, and chronic back pain. Opioid analgesics, however, are not first-line agents for the long-term management of chronic nontumor-related pain.