Pain is likely the most common symptomatic complaint in medicine; an understanding of its pathophysiology is critical to interpreting it in patients.

When thermal, mechanical, or chemical stimuli reach a noxious intensity suggestive of injury, they become detected by nociceptors, which are a subpopulation of peripheral nerve fibers found in the skin, joints, viscera, bone, and muscle.

The damaged tissue releases and produces numerous factors which in turn activate nerve endings. These factors include globulin, protein kinases, arachidonic acid, histamine etc. (1)

Pain has been suggested to act as a stressor during aging and it accelerates functional and health status decline. Older adults suffering from pain are less physically active, experiences more comorbidities, and worse functional mobility than older adults without pain. (3)

Localization of pain

Nociceptors are present in the viscera, skin, joints, bone, and muscle: an important consideration is that there are no nociceptors found in the CNS; this is the rationale for why awake craniotomy is possible, and not painful for the patient.

It is also necessary to appreciate that the specific sensory modalities leading to nociception differ depending on the type of tissue:

• In skin, noxious stimuli are commonly thermal, mechanical (e.g., a cut), and chemical (e.g., exogenous allergens)
• In the joints, noxious stimuli commonly derive from mechanical stress (e.g., excessive joint torque) and chemical inflammation
• In the visceral organs: mechanical distension, traction as well as chemical irritants are usually responsible for nociceptive signals
• In the muscles, strenuous mechanical exertion (e.g., blunt force, over-stretching) and chemical modalities are most common

Nociceptive signal transduction to the brain is what elicits the perception of pain. While in typical situations, nociception does typically precede perception of pain, there are clinical circumstances in which these interfaces do not overlap. Nociception can occur without subsequent awareness of pain, and pain can be present without a measurable underlying noxious stimulus. For instance, the former may be observable following severe trauma when victims are remarkably pain-free despite massive injury; the latter may be observable with individuals suffering from functional pain syndromes who report substantial pain without signs of physical damage.

The perception of pain is subjective

There are a number of psychological processes behind pain perception. Attentional orienting to the painful sensation and its source can serve to heighten the painful experience. For instance, patients with somatic preoccupation and hypochondriasis are found to over-attend to bodily sensations, amplifying them as pain.

Testing the pain

The complex, multi-faceted and subjective nature of pain makes it rather challenging to measure clinically. Over the past few decades, a number of validated measures have undergone development in an effort to assist research on the mechanisms of pain and outcomes of measurement. For acute pain, relevant in the management of surgical procedures or acute mental illness, the visual analogue scale (VAS) and numeric rating scale (NRS) are most frequently used to assess the intensity of pain. For chronic pain, multidimensional tools such as the McGill Pain Questionnaire (MPQ) and the Brief Pain Inventory (BPI) have been developed.

Currently, the tools as mentioned above are used mainly in the research setting, though new experimental measures of pain, for instance, neuroimaging as an objective measurement, are being proposed.

Clinical Signifiance

The characteristics of a patient’s pain offer indications regarding its pathogenesis. A brief explanation of classes of pain is thus useful clinically to assist in the management of pain as a symptom and possible diagnosis of the underlying condition.

• Acute pain: At the site of local tissue injury, the activation of nociceptive transducers contributes to this form of pain. The local injury environment may further alter the characteristics of nociceptors, central connections, and the autonomic nervous system.

• Chronic pain: Persistent pain is frequently related to conditions (e.g., diabetes mellitus, arthritis, and tumor growth) which potentiates chronic tissue inflammation or alteration of the properties of peripheral nerves (neuropathic). Given the unrelenting nature of chronic pain, expectations are that external factors such as stress, emotions, and the environment may produce a summative effect with the damaged tissue to enhance the intensity and persistence of the pain.

• Somatic pain: This form of pain may be acute or chronic and is pain activated by the nociceptors in the cutaneous or deep tissues. In the case of cutaneous somatic pain, for instance, in the case of a skin cut, it is described as sharp or burning and is well localized. In the case of somatic pain arising from the deep tissues, such as in the joints, tendons, and bones, it is described as more throbbing or aching and is less localized.

• Visceral pain: This pain arises mainly from the viscera and deep somatic structures (e.g., pain from the gastrointestinal tract). Visceral pain that is not distinctly localized is carried by the C fibers from the deep structures to the spinal cord.

• Neuropathic: This persistent pain is often a consequence of damage to these nerve fibers, leading to increased spontaneous firing or alterations in their conduction or neurotransmitter properties.

• Allodynia: Pain resulting from a typically harmless stimulus is referred to as allodynia. Though the mechanism is not fully understood, it is thought to potentially arise from 1) sensitization of the skin, leading to a decreased threshold of silent nociceptors or 2) damage to peripheral neurons inducing structural changes leading touch-sensitive fibers to reroute and form synapses in areas of the spinal cord that normally receive pain input.

• Hyperalgesia: Occurs when noxious stimuli generate an exaggerated pain response. Similar mechanisms as proposed in the case of allodynia, with patients demonstrating amplification of pain or hyperalgesia, as well as a lengthened persistence of the pain.

• Referred pain: When there is pain perception at a location other than the site of the painful stimulus, it is known as referred pain. The classical example of referred pain involves pain brought down the neck, shoulders, and back following a myocardial infarction. There is no current consensus regarding the true mechanisms behind referred pain, and there are several theories.  Referred pain may be visceral or somatic, with the former describing pain from an organ and the latter describing pain from the deep tissues such as muscles or joints. In the Ruch’s 1961 convergent-projection theory, where afferent visceral sensory pain fibers and somatic fibers enter the same spinal dorsal root ganglia segments of the spinal cord, causing the CNS to misinterpret the pain as arising from somewhere on the body wall rather than from the viscera. Somatic referred pain occurs when spinal structures such as discs or joints receive a noxious stimulus, and the pain is subsequently interpreted to be localized in the deep tissues – most commonly those of the lower extremity. This is proposed to occur by neurons that innervate these somatic tissues converging with nociceptive afferent neurons on the same second-order neurons in the spinal cord. (1)

How to relieve pain

Over-the-counter medications can be used to relieve pain, but in moderation, as they can have side effects. Additionally, they can interact with other medications, supplements, or foods we take.

Over-the-counter (OTC) pain relievers include:

• Acetaminoiphen
• Nonsteroidal anti-inflammatory drugs (NSAIDs)

Both acetaminophen and NSAIDs reduce fever and relieve pain caused by muscle aches and stiffness, but only NSAIDs can also reduce inflammation (swelling, heat, redness related to an injury, and irritation). Acetaminophen and NSAIDs also work differently. NSAIDs relieve pain by reducing the production of prostaglandins, which are hormone-like substances that cause pain and inflammation. Acetaminophen works on the parts of the brain that receive the “pain messages.”

Using NSAIDs regularly, especially at high doses, increases the risk of heart attacks and strokes and can also cause stomach ulcers and bleeding. They can also cause kidney problems. Taking acetaminophen regularly at high doses can cause a liver problem. Taking a large amount at once intentionally or accidentally is a medical emergency.

Prescription medicines to treat pain include:

• Corticosteroids
• Opioids
• Antidepressants
• Anticonvulsants (anti-seizure medications)
• NSAIDs
• Lidocaine patches (2)

Pain management in a multidisciplinary way

Managing pain in older adults is a complex task due to the high prevalence of multiple comorbidities, polypharmacy, and, in general, socio-psychological vulnerability. Moreover, drugs-related adverse events (AEs) can be potentially harmful and hardly manageable in older adults (e.g., non-steroidal anti-inflammatory drugs and opiates AEs), even though drug prescriptions are generally individualized and tailored to patients’ health and social status. Based on this, pain management in the elderly may be more effective when the intervention is based on a multidisciplinary method (e.g., psychological treatment, exercise program, complementary medicine, nutrition, and dietary supplementation).

Nutrition and nutraceuticals have proved to have a role in pain management and to help the patient overcome chronic pain, thereby improving the quality of life. Researchers have identified several nutritional components that may improve chronic pain syndromes through anti-oxidant and anti-inflammatory activities.

In subjects with age-related sarcopenia and frailty, specific nutritional and nutraceuticals interventions may play a relevant role in a long-term program of pain management. In particular, significant beneficial involvement of specific nutrients (i.e., proteins and amino acids, omega-3 fatty acids, magnesium and vitamin D), botanicals (curcumin and ginger) have been described.

The results of this study are useful to develop best-practice guidelines for a multidisciplinary management of pain that involve nutritional recommendation to support health professionals during the design of a personalized therapy. (3)

Among the supplements that we would like to suggest, there is the My Antioxydant by Meetab, whose description can be found here:

https://www.meetab.it/my-antioxidant-integratore-naturale-antiossidante

Bibliography

1. https://www.ncbi.nlm.nih.gov/books/NBK539789/
2. https://www.webmd.com/pain-management/guide/pain-relievers
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151174/