Pain
Pain [3, 4, 57] is a distressing and unpleasant sensation perceived by the organism usually in response to a harmful stimulus. It usually serves as a warning signal from the body to indicate a threat to its physical integrity.
Pain can also refer to emotional suffering (for example, following a death); however, this type of pain will not be addressed here. Even though it is an unpleasant experience, pain circuits play a vital role in our survival [48, 187], as this sensation forces us to act, often instinctively, to escape potential danger.
Pain is the primary symptom in most diseases [208, 209]. Its clinical description is of major interest for reaching an accurate diagnosis and, subsequently, an appropriate remedy. However, pain can be so excessive and intolerable that it becomes a disease in itself. It is essential to implement targeted interventions that alleviate patient distress.
Pathophysiology of pain :
From the Periphery to the CNS:
The nociceptive message [107] (painful) results from a painful stimulus at the nerve endings of cutaneous [69], muscular, articular, or visceral structures. This message is then carried by afferent nerve pathways to the CNS [1, 4].
Polymodal nociceptors (activated by mechanical, thermal, and chemical stimuli) and unmyelinated C fibers play a major role in detecting, encoding intensity, and transmitting cutaneous pain. These C fibers are unmyelinated with a diameter <1 µm [3] and a slow conduction velocity <2 m/s. Other types of fibers also participate in the conduction of nociceptive signals, such as A-delta fibers (thinly myelinated) [57].
After traveling through the peripheral nerves, the nociceptive afferent fibers reach the central nervous system [41] at the level of the posterior roots of the spinal cord or, for cranial nerves, at the brainstem. Substance P (the primary neurotransmitter of pain) and glutamate excite the neurons of the dorsal horn of the spinal cord [1, 38, 107]. The nociceptive impulse then follows the spinothalamic (extralemniscal) pathway [145], which is specific to thermo-nociception.
Modulation of nociceptive messages :
Once the nociceptive message is transmitted from the periphery to the CNS, it is modulated by different control mechanisms [35].
Afferent fibers (A-alpha and A-beta) that transmit tactile messages inhibit nociception at the spinal level. This explains our tendency to touch the hurt area immediately after the accident. These inhibitory phenomena can be presynaptic or postsynaptic (Gate Control Theory [39]).
In the brainstem, there are neurons that give rise to descending inhibitory pathways [38, 107] (for example, those in the periaqueductal gray [3]). By blocking nociceptive pathways, these neurons induce analgesia in the painful area.
Different types of pain [69]:
According to the Mechanism of Pain:
Nociceptive pain :
This represents the classic model of reception, transmission, and perception of pain according to the mechanisms mentioned above.
Neurogenic pain :
This refers to pain that does not result from tissue damage but is due to an interruption of nociceptive pathways, leading to a disturbance in the transmission system [207].
Psychogenic pain :
This refers to pain for which there is no organic explanation [207].
Referred Pain :
The fibers of the spinothalamic pathway sometimes receive convergent afferents from both the skin and certain viscera. When a nociceptive impulse is received, the brain attributes the source of the stimulus to the skin, which is more frequently stimulated. This is the case, for example, during a myocardial infarction "heart attack", where pain is felt in the left hand and the mandible, even though there is no injury there [3, 209].
Depending on the course of the pain:
- Acute pain [48].
- Chronic pain [69].
Pain Assessment :
Simple Verbal Scale (SVS) :
The patient is asked verbally to evaluate their pain according to 4 or 5 categories, resulting in a score: 0: No pain, 1: Mild, 2: Moderate, 3: Severe, 4: Extremely severe [210].
Numerical Rating Scale (NRS) :
This allows the patient to rate their pain on a scale where the minimum score is 0 and the maximum, representing intolerable pain, is 10 [208].
Visual Analog Scale (VAS) :
This is a ruler featuring a subjective line on one side and a 100 mm scale on the other. The patient draws a line or moves a slider according to the intensity of the pain, ranging from (no pain) to (worst imaginable pain). The healthcare provider matches the notation on the back to the displacement of the slider [91, 179].
Other Multidimensional Methods :
This category includes several types of questionnaires and behavioral scales. While subjective, these assessment tools are essential for clinical orientation and monitoring pain progression [208].
Analgesic treatments :
Therapeutic measures must primarily target the source of the pain but must also aim for patient relief [69]. The World Health Organization (WHO) has classified different analgesic substances into three levels based on their activity. It is recommended to follow this step-by-step strategy in pain management [91].
Level 1 :
Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and noramidopyrine. For pain judged as mild or moderate by a physician, these drugs should be prescribed first. They act primarily by inhibiting cyclooxygenase, an enzyme responsible for a cascade of chemical reactions that lead to pain. The most frequent side effects of these drugs are gastric, though other very serious disorders can occur in cases of overdose.
Level 2 :
Weak opioid analgesics [211], which are derivatives of opium and morphine, such as codeine, dihydrocodeine, dextropropoxyphene, and tramadol. Codeine and dextropropoxyphene are often combined with Step 1 analgesics because their modes of action are different and complementary, creating a synergistic effect. These substances act on the CNS via specific receptors responsible for pain suppression. The primary side effects include constipation, drowsiness, nausea, vomiting, and respiratory difficulties. These compounds carry a risk of physical dependence.
Level 3 :
Strong opioid analgesics, such as morphine [48, 211] and its derivatives. These drugs have the same characteristics and the same mode of action as the previous ones but are more powerful. They are used for severe pain or pain resistant to Step 2 analgesics. They share the same side effects as weak opioid analgesics and can lead to the same issues with dependence.