Pain is a complex physiological and psychological phenomenon that is subjective in nature. Pain is still one of the most challenging prevalent problems. Worldwide, the prevalence of chronic pain reaches up to 30%. The WHO estimates that as many as 1 in 10 adult individuals are newly diagnosed with chronic pain each year. In the United States, it was estimated that 51.6 million people experience chronic pain. In Arabian Gulf region 55% of chronic low back ache patients were classified to have neuropathic pain. The situation is approximately the same or even worse in the developing countries, because of under diagnosed and undertreated with limited resourses. Chronic pain is a leading cause of disability and disease burden globally.
Pain is derived from latin word “Poena” meaning punishment or penalty. According to the International Association for the study of Pain (IASP), Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”. Pain may not be directly proportional to amount of tissue injury.
Types of Pain
Pain is classified on the basis of duration, location, intensity and etiology. Depending on its duration pain can be acute and chronic. Acute pain is defined as “pain which has a sudden onset with varied intensity lasting for less than three months”. Chronic pain is defined as “pain that lasts for more than three months which may or may not have an underlying pathology to explain the patient’s suffering”.
Depending on intensity of pain (standard scales), pain can be mild, moderate and severe. Depending on etiology (neuro-physiological mechanisms) pain can be divided into 2-major types;
- Nociceptive pain- is from tissue damage. Further, nociceptive pain can be divided into somatic and visceral pain. Somatic pain is pain resulting from excitation and sensitization of nociceptors in tissues, such as skin, bones, joints, tendons and muscle fasciae. It is intermittent or constant and it could be described as sharp or dull aching, clearly located or poorly localized, stabbing, or throbbing. Further it can be subdivided into superficial and deep pain. In contrast, visceral pain involves gut and hollow organs such as heart, stomach, or liver. This pain is diffuse, for this reason it is referred to other location. However, visceral pain not always linked to visceral injury; for instance, stretching of the bladder can cause this pain.
- Neuropathic pain- is a chronic pain and caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain is usually described as Paresthesia(pins and needles), Burning, Numbness , Shooting(electrical shock), Hyperalgesia , Allodynia. Further it can be subdivided into Peripheral Neuropathic Pain (PNP) and Central Neuropathic Pain(CNP). Peripheral neuropathic pain- follows damage or sensitization of peripheral nerves. The peripheral nervous system includes nerves and ganglia that are located outside the brain and the spinal cord. PNP can be caused by diabetic peripheral neuropathy, peripheral nerve injuries, postherpetic neuralgia, radicular pain, trigeminal neuralgia, chemotherapy-induced peripheral neuropathy and phantom limb pain. Central neuropathic pain- results from malfunctioning of nerves in Central Nervous System(CNS). The CNS includes the brain, brainstem, and spinal cord. CNP is most commonly caused by multiple sclerosis, poststroke pain, parkinson disease and spinal cord injuries.
Physiology/Transmission of Pain
Nociception is the transfer of information from the site of tissue damage to the CNS. However, nociceptive pain is caused by activation of chemoreceptors, mechanoreceptors, and thermoreceptors, depending on the cause of damage/ injury. Pain receptors, or nociceptors, are located in the skin and are responsible for transmitting pain signals from the periphery to the CNS. Pain is transmitted from the periphery to the CNS via 4-main processes; Transduction, Transmission, Perception, and Modulation.
During the transduction phase, noxious, thermal, mechanical or chemical stimuli are trigger the release of nociceptor-sensitizing substances such as bradykinin, serotonin, histamine, prostaglandins, and substance P. The nociceptor-sensitizing substances generate a current, known as an action potential. Throughout the transmission phase, the electrical signal information is transmitted along two types of peripheral nerve fibers (A and C) delta to the dorsal horn of the spinal cord.
For illustration, A-delta fibers are covered by a fatty myelin sheath that isolates the fibers, ensuring that the signals travel quickly. These nerves are responsible for the localized, sharp, stabbing pain that initially happens with injuries, alerting the person to the damage. C-delta is unmyelinated fibers so the signals travel slower and create dull, aching pain that continues after an injury trying to foster rest and prevent further damage.
Once the stimuli are converted into electrical signals, the information is then transmitted to the spinal cord and brain via the afferent nociceptor. The afferent nociceptor has its cell body in the dorsal root ganglion; each dorsal root ganglion has distinct sensory cell bodies that encode and then transmit information into the dorsal horn of the spinal cord. Once in the dorsal horn, the fibers ascend approximately 2 levels before they synapse on second-order neurons.
These second-order neurons then decussate across the anterior white commissure and ascend as the lateral spinothalamic tract. The spinothalamic tract ascends through the brainstem as the spinal lemniscus until it synapses on the ventral posterolateral nucleus of the thalamus. Axons from the thalamus then project to the somatosensory cortex of the brain. Perception of pain mainly begins at the level of the thalamus and the cortex and is the subjective appreciation of the quality, location, and intensity of pain.
The perception of pain can be modulated by descending inhibitory input from the brain that modulates nociceptive transmission at the level of the spinal cord. Modulating nerve fibers can release inhibitory substances at the dorsal horn, such as endogenous opioids (e.g., endorphins, enkephalins), and norepinephrine, which bind to receptors on primary afferent or dorsal horn neurons and inhibit the transmission of pain.
The pathophysiology of neuropathic pain is complex and number of mechanisms are believed to be involved as; The mechanism that may contribute to neuropathic pain in CNS is central desensitization. This is develops when the part of nociception that should disappear when healing accomplished, continues and become permanent. The increased receptive field for peripheral nerve input may continue, interneurones might die, and there may be an excess in neurotransmitter release. Furthermore, the descending inhibitory mechanism that tries to modulate pain may also be affected in people with neuropathic pain. This means that endogenous opioid production or the pathways that decrease pain may be not effective.
Further, Peripheral nerves may also be affected by some changes as a result of nerve damage. Increased excitability and spontaneous firing of neurons may occur after injury. During the trails of repair and regeneration, propagation or enlarged nerve tissue forms a structure called a neuroma. Yet, neuromas can produce random signals along the nerve pathway.
Pain Assessment: Methods of pain assessment are beginning with comprehensive history intake, physical examination and questioning on characteristic of pain. Pain assessment tools should be used to aid diagnosis and determine the effectiveness of analgesics and interventions. A simple unidimensional tool; e.g. 0-10 Numerical Pain Scale, where 0=no pain; 1,2,3=mild pain; 4,5,6=moderate pain; 7,8,9,10=severe pain and above 10=unbearable pain. The Modified WHO Analgesic Ladder has developed 4-steps model to guide analgesic choice depending on the severity of the patient’s pain.
Basic Principles of Pain Management
Pain management is complex due to several causes, including the mechanisms of pain, classification, individualization, lack of commonly accepted guidelines, knowledge, psychological and social factors. Pain management is well known since many decades. It has been improved a lot lately and is starting to involve plenty of diverse methods. Certainly, the management of pain is a multidisciplinary task, the control of pain can be pharmacological and non-pharmacological interventions, or a combination of these two therapies.
- Pharmacological Methods: Pain that affects patients’ physical function or their quality of life should be recognized as a significant problem. Elderly, cancer, postoperative, and traumatic patients with functional impairment or diminished quality of life are ideal candidates for pharmacological therapy. However, the intervention decision either to be pharmacologic or non-pharmacologic is based on a cautious weighing of risks and benefits. Pharmacotherapy are generally classified into two lines therapy which are first line (non-opioid analgesics) and second line(opioid analgesics).
- Non-Opioid Drugs: Generally, a recommended practice by clinicians is usually to start with non-opioid analgesics such as Acetylsalicylic acid, Acetaminophen, Non Steroidal Anti-Inflammatory Drugs(NSAIDs), and gradually advance to more potent analgesics till the pain is relieved. Acetaminophen is useful as a primary analgesic or in combination with other drugs for treating mild to moderate pain. Aspirin and other related compounds constitute a category of drugs known as NSAIDs. The NSAIDs are useful analgesics for managing mild to moderate pain, particularly of somatic origin. However, it was reported that the use of acetaminophen and an NSAID as a combination was superior to use acetaminophen alone.
However, American Heart Association recommended acetaminophen, Acetylsalicylates and even opioids instead of NSAIDs and particularly COX-2 agents in patients with coronary artery disease (CAD). Further, in some situations, NSAIDs can cause acute renal failure due to the inhibition of the biosynthesis of prostaglandins involved in the maintenance of renal blood flow.
Opioid Drugs- Opioid analgesics are commonly used as the first-line treatment of moderate to severe pain either in acute, chronic, cancer related or at the end of life.
However, opioids are very effective analgesics in the short term, but the evidence showed some limitations of efficacy in long-term. As a consequence, patients on opioids therapy should have regular check up for both, drug efficacy and patients’ tolerability. Opioid drugs which are currently used in clinical practice such as Tramadol, Tapentadol, Codeine, Oxycodone, Morphine, Buprenorphine, and Fentanyl.
Tramadol is a centrally acting as μ -opioid receptor agonist. It acts as a weak nor-epinephrine and serotonin reuptake inhibitor. It is actually indicated for the management of moderate to severe pain. Tramadol is contraindicated in seizure patients, because of increasing risk of seizures. Tapentadol is a µ-receptor agonist and norepinephrine inhibitor.
Morphine deemed as the drug of choice for treatment of moderate to severe cancer pain. Morphine is primarily effective for the treatment of nociceptive pain. On the other hand, it was found that Morphine could be effective for the treatment of neuropathic pain particularly when combined with antidepressants and the gabapentinoids. Fentanyl is a fast acting lipophilic opioid, and it is available in several forms such as parenteral, transmucosal, and transdermal formulations.
Not all types of pain, particularly neuropathic pain, respond to Acetaminophen, NSAIDs or Opioids, because they do not target the underlying cause of neuropathic pain. Patients with neuropathic pain may be prescribed adjuvant therapies. In Neuropathic pain first-line treatments include; Tricyclic antidepressants (TCAs), serotonin norepinephrine reuptake inhibitors (SNRIs), gabapentinoids, and topical medications. These medications are trialed for 4 to 6 weeks. If there is an exacerbation or inadequate response to first-line agents, then second-line agents opioids (tramadol) or a combination of first-line agents is trialed for 4 to 6 weeks.
Tricyclic antidepressants especially Amitriptyline and Nortriptyline, inhibiting the reuptake of serotonin and norepinephrine in the spinal dorsal horn. TCAs are thought to work by activating a descending inhibitory response. Research has shown that these drugs exert an analgesia effect when taken at lower doses. International guidelines of neuropathic pain have made the use of SNRIs a first-line treatment, especially duloxetine and venlafaxine. These drugs enable descending inhibition by blocking serotonin and norepinephrine reuptake.
Anticonvulsant medications; such as gabapentin, pregabalin and carbamazepine, are believed to treat neuropathic pain by stabilizing membranes and also by depressing segmental and descending excitatory pathways. A multimodal approach to treat neuropathic pain has been shown to be effective, so topical agents can especially help when combined with other therapies. Topical agents such as lidocaine and capsaicin have been shown to be effective in neuropathic pain.
Non-Pharmacological Methods
Non-pharmacologic treatments are important adjuncts to treatment modality for patients with pain. It may be used independently with mild pain or in addition, it can be used along with pharmacological therapy as a complementary option for moderate to severe pain. Non-pharmacological treatments are cognitive behavioral therapy, acupuncture, emotional support, physical exercise, massage, bed rest, manipulation and mobilization, traction, superficial Heat and cryotherapy. A nonpharmacologic approach to neuropathic pain involves neuromodulation. Transcutaneous Electrical Nerve Stimulation (TENS), Percutaneous Electrical Nerve Stimulation (PENS) are nerve stimulators and involves the electrical stimulation of the nervous system to modify a person’s perception of pain.
Recent Advances in Pain Management
Pain adjuvants such as; corticosteroids, local anesthetics, muscle relaxants, bisphosphonates, N-methyl-D-aspartate(NMDA) receptor antagonists such as Ketamine; prevents central sensitization. Dexmedetomidine, an alpha-1 agonist, used as sedative and analgesic agent in intensive care settings. If pain persists or worsen, the Modified WHO Analgesic Ladder step-4 is focusing on Interventional and Minimally Invasive Procedures for managing persistent pain, including Nerve blocks, Epidural blocks, Patient Controlled Analgesia(PCA), Platelet-Rich Plasma(PRP) injections, Radiofrequency Ablation(RFA), TENS Unit and Spinal Cord Stimulation(SCS).
Pain management is a dynamic and multi-faceted process that goes beyond simply alleviating discomfort. It is important for health care providers to understand the pathophysiology and management of pain for the provision of appropriate care to patients. In general, pain is underestimated by healthcare providers. This underestimation might lead to poor management which negatively affects patient’s outcomes, quality of life, and satisfaction.
(The author is Anesthesiologist and currently working at Govt. S.D.H. yaripora, Kulgam. Feedback: [email protected])
