Chronic pain

Chronic pain is defined as pain that persists longer than the temporal course of natural healing, associated with a particular type of injury or disease process.

The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." It is important to note that pain is subjective in nature and is defined by the person experiencing it, and the medical community's understanding of chronic pain now includes the impact that the mind has in processing and interpreting pain signals.

Functional anatomy

The anatomy of the nociceptive system can be grossly divided into the peripheral and central nervous system. The peripheral nervous system consists of small myelinated and unmyelinated nerve fibers. These nerve fibers converge into a region of the spinal cord referred to as the dorsal horn. The dorsal horn is the first relay station in pain signal transmission. The next element of pain transmission includes nerve fibers that then travel to the thalamus. From the thalamus the next order of neurons ascend to the limbic system and sensory cortex. This accounts for the affective elements and discriminative of pain respectively.


Nociceptors convey information regarding damage or trauma from the body to the central nervous system, a process called nociception, where it is interpreted by the brain as pain. Nociception occurs in any tissue or organ in which pain signals arise secondary to a disease process or trauma. The nociception can also occur if there is dysfunction or damage to nerves themselves.


Under persistent activation nociceptive transmission to the dorsal horn may induce a wind up phenomenon. This induces pathological changes that lower the threshold for pain signals to be transmitted. In addition it may generate nonnociceptive nerve fibers to respond to pain signals. Nonnociceptive nerve fibers may also be able to generate and transmit pain signals. In chronic pain this process is difficult to reverse or eradicate once established.


Nociception (pain) may arise from injury or disease to visceral, somatic and neural structures in the body. More broadly pain is described as malignant or non-malignant in origin.


Pain may be a response to injury or any number of disease states that provoke nociception. Advances in imaging studies and electrophysiological studies allow us to gain a deeper insight into the characteristics and properties associated with the phenomenon of chronic pain.

Related sequelae

Chronic pain may cause other symptoms or conditions, including depression and anxiety. It may also contribute to decreased physical activity given the apprehension of exacerbating pain. Conversely it may itself have psychosomatic or psychogenic component to its cause. Very little work has been done on the cognitive effects of chronic pain, with most of the publications focussing on the effects of cognition on pain but only 5% examining the effects of pain on cognition.


Chronic pain impairs the ability to direct attention, in particular when compared to peers with low intensity or no chronic pain, people with high-intensity chronic pain have significantly reduced ability to perform attention-demanding tasks. The pain sensations appear to strongly capture the attention of people with chronic pain; tests assessing the ability to attend show poorer performance than peers who do not experience chronic pain on all tests demanding attention. The exception is found with tasks that are highly demanding of attention, where performance between the two groups is equivalent. In experimental testing, two-thirds of individuals with chronic pain demonstrate clinically significant impairment of attention, independent of age, education, medication and sleep disruption. Individuals with the highest levels of pain showed greatest disruption of memory traces, suggesting that pain diminishes working memory.


It is rare to completely achieve absolute and sustained relief of pain. Thus, the clinical goal is pain management. Pain management is often multidisciplinary in nature. A recent journal article by Gatchell and Okifuji recognizes the importance of comprehensive pain programs(CPPs) in the management of chronic pain. They summarize their findings as follows: "CPPs offer the most efficacious and cost-effective treatment for persons with chronic pain, relative to a host of widely used conventional medical treatment."


In the treatment of chronic pain, whether due to malignant or benign processes, the three-step WHO Analgesic Ladder is often used. This provides guidelines for stepping up the amount of analgesia and maintains a general basis that is used in a number of countries around the world to manage chronic pain conditions. The exact medications recommended will vary with the country and the individual treatment centre, but the following gives an example of the approach to treating chronic pain with medications. If, at any point, treatment fails to provide adequate pain relief, then the doctor and patient move onto the next step.

Mild pain

Paracetamol (acetaminophen), or a non steroidal anti-inflammatory drug such as ibuprofen

Mild to moderate pain

Paracetamol, an NSAID and/or paracetamol in a combination product with a weak opioid such as hydrocodone; used in combination, may provide greater relief than their separate use.

Moderate to severe pain

Morphine is the gold standard choice, followed by Oxycodone, Fentanyl in the form of a transdermal patch designed for chronic pain management, Diamorphine, hydromorphone or methadone are used less frequently.

Pethidine is not recommended for chronic pain management due to its low potency, short duration of action, and toxicity associated with repeated use.


Opioid medications can provide a short, intermediate or long acting analgesia depending upon the specific properties of the medication and whether it is formulated as an extended release drug. Opioid medications may be administered orally, by injection, via nasal mucosa or oral mucosa, rectal, transdermal, intravenously, epidurally and intrathecally. In chronic pain conditions that are opioid responsive a combination of a long acting or extended release medication is often prescribed in conjunction with a shorter acting medication for break through pain (exacerbations).

Most opioid treatment is oral (tablet, capsule or liquid), but suppositories and skin patches can be prescribed. An opioid injection is rarely needed for patients with chronic pain.

Although opioids are strong analgesics, they do not provide complete analgesia regardless of whether the pain is acute or chronic in origin. Opioids are efficacious analgesics in chronic malignant pain and modestly effective nonmalignant pain management. However, there are variable associated adverse effects, especially during the commencement or change in dosing and administration. When opioids are used for prolonged periods drug tolerance, chemical dependency and (rarely) addiction may occur. Chemical dependency is ubiquitous among opioid therapy after continuous administration; however, drug tolerance is not well studied in patients on long term opioid therapy. Addiction rarely occurs as a result of opioid prescription, but they are abused by some individuals, which can cause concern to health care providers. Diversion of opioid medications is another concern for health care providers.

Non-steroidal anti-inflammatory drugs

The other major group of analgesics are Non-steroidal anti-inflammatory drugs (NSAID). This class of medications does not include acetaminophen, which has minimal anti-inflammatory properties. However, acetaminophen may be administered as a single medication or in combination with other analgesics (both NSAIDs and opioids). The alternatively prescribed NSAIDs such as ketoprofen and piroxicam, have limited benefit in chronic pain disorders and with long term use is associated with significant adverse effects. The use of selective NSAIDs designated as selective COX-2 inhibitors have significant cardiovascular and cerebrovascular risks which have limited their utilization.

Antidepressants and antiepileptic drugs

Some antidepressant and antiepileptic drugs are used in chronic pain management and act primarily within the pain pathways of the central nervous system, though peripheral mechanisms have been attributed as well. These mechanisms vary and in general are more effective in neuropathic pain disorders as well as complex regional pain syndrome. Drugs such as Gabapentin have been widely prescribed for the off-label use of pain control. The list of side effects for these classes of drugs are typically much longer than opiate or NSAID treatments for chronic pain, and many antiepileptics cannot be suddenly stopped without the risk of seizure.

Other Adjuvant & Atypical Analgesic Agents

Other drugs are often used to help analgesics combat various types of pain and parts of the overall pain experience. In addition to gabapentin, the vast majority of which is used off-label for this purpose, orphenadrine, cyclobenzaprine, trazadone and other drugs with anticholinergic properties are useful in conjunction with opioids for neuropathic pain. The latter three drugs are also muscle relaxants and are therefore particularly useful in painful musculoskeletal conditions. Clonidine has found use as an analgesic for this same purpose and all of the mentioned drugs potentiate the effects of opioids overall.

Interventional therapy

Pulsed radiofrequency, neuromodulation, direct introduction of medication and nerve ablation may be used to target either the tissue structures and organ/systems responsible for persistent nociception or the nociceptors from the structures implicated as the source of chronic pain.

An intrathecal pump used to delivery very small quantities of medications directly to the spinal fluid. This is similar to epidural infusions used in labour and postoperatively. The major differences are that it is much more common for the drug to be delivered into the spinal fluid (intrathecal) rather than epidurally, and the pump can be fully implanted under the skin. This approach allows the drug to be delivered directly to the site of action, ie the spinal cord, and so allows a higher dose to be given with less systemic side effects.

A spinal cord stimulator is an implantable medical device that creates electric impulses and applies them near the dorsal surface of the spinal cord provides a paresthesia ("tingling") sensation that alters the perception of pain by the patient.


As alluded to earlier there are other modalities used in the treatment of chronic pain. These include: physical modalities such as thermal agents and electrotherapy. Complementary and alternative medicine, therapeutic exercise and behavioral therapy are also utilized autonomously or in tandem with interventional techniques and conventional pharmacotherapy. This is most often structured in a multidisciplinary or interdisciplinary program.

Behavioral therapy

Applied behavior analysis treats pain as mixture of respondent and operant conditioning in which normal tissues learn to fire pain responses in the presence of specific environmental antecedents and consequences. The model was first proposed by Fordyce in 1976. There is mixed support for behavioral treatment of pain, with many studies reporting positive results, though a review of studies in 2005 suggested that though behavioral can be an effective and economical means of treating chronic pain, a substantial portion of patients do not benefit from behavior therapy, that effects are rather modest, and there is little evidence to support different treatment modalities have different effects.


Biofeedback based on behavioral principles has shown some success for chronic pain, demonstrating greater improvement in one study than peers undergoing cognitive-behavioral therapy and conservative medical treatment, though a different study showed improvements over wait-list controls but no difference between biofeedback and cognitive-behavioral therapy.

See also

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