Clinical Diagnosis and Treatment of Chronic Pain

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1		Sadiq Rahman	--	2386	2023-12-28 20:33:51	\|
2	Reference format revised.	Lindsay Dong	Meta information modification	2386	2023-12-29 02:09:59	\|

This entry is adapted from the peer-reviewed paper 10.3390/diagnostics13243689

Pain medicine is a multidisciplinary and multimodal approach to help patients manage chronic pain. The definition of chronic pain has evolved to become less “non-specific” and to help aid in the proper classification of the disease. While the term can often be too generalized when describing a wide array of conditions, the future of chronic pain diagnosis and treatment is becoming more personalized and precision based. More optimized and specific chronic pain diagnoses can help avoid pooling together heterogenous conditions.

chronic pain pain diagnostics pain classification pain approach

1. Defining Chronic Pain

The most common symptom reported to health care providers is pain. Chronic pain is often used as an umbrella term for a wide range of painful conditions from nonspecific lower back pain to fibromyalgia to complex regional pain syndrome (CRPS). While acute pain may serve an adaptive role, chronic pain has been widely considered to be clinically maladaptive, that “neither protects nor supports healing and repair” ^[1]. Chronic pain was previously defined as pain persisting past a normal healing time and lacking the advantage of acute pain’s warning function ^[2].

It is often defined as pain that persists longer than “normal healing” and widely agreed to be at least three months in duration. Chronic pain also has been used as a label for a patient’s condition when underlying causes of pain are unclear or have been unidentified. This reinforces the need for more precise and updated methods of diagnosis and treatment for the many patients who encounter chronic pain.

The International Association for the Study of Pain (IASP) characterizes pain as an unpleasant sensory and emotional experience associated with, or resembling, actual or potential tissue damage ^[3]. The IASP definition of chronic pain has become widely adopted by health care professionals and academic researchers and even adopted by professional organizations such as the World Health Organization (WHO).

The need for adequate revision for chronic pain diagnoses in the International Classification of Diseases (ICD) system has also been expressed as it is crucial for not only improvements in treatment but also for launching relevant research programs. Current iterations and classifications of chronic pain conditions are sometimes poorly defined and arbitrarily distributed in the ICD system ^[4]. As recently as the release of the ICD-10, chronic postsurgical and posttraumatic pain was not being represented; it was only defined as of 2022 within the ICD-11 ^[5].

Thoughts, emotions, and stress also affect the perception of pain, so a biopsychosocial assessment of pain helps provide a more complete definition and overview of conditions associated with chronic pain ^[6]. Neuroscience research indicates pain pathways in the central nervous system (CNS) often work in conjunction with emotions. Pain pathways can also be stimulated by peripheral tissues and traumatic experiences ^[7].

The biopsychosocial model views illness as a complex interaction between psychological, social, and biological factors ^[8]. This has also led to the development of an interdisciplinary pain management approach. Conceptualizing, assessing, and treating chronic pain would be incomplete without a sophisticated understanding of the emotional states and processes linked with the condition ^[9].

2. Diagnosing Chronic Pain

Properly diagnosing chronic pain is crucial to the successful management of the condition. In the field of headache research, strict criteria for headaches such as migraines help dictate diagnosis and treatment and facilitate additional inquiry. As previously discussed, chronic pain is currently defined as pain that persists or recurs for more than 3 months, consistent with temporal cutoffs associated with other chronic diseases ^[10]. The 3-month criterion is a common temporal cutoff for chronic conditions. This allows chronic pain diagnoses to remain consistent with criteria of many other chronic health conditions, which facilitates a uniform measure across clinical practice, health statistics, and academia.

Reaching a timely, accurate diagnosis for chronic pain is important to avoid progression towards a chronic disease. One study examining 180 patients with complex regional pain syndrome (CRPS) found that a long a time between onset and diagnosis was predictive for late recovery and the progression of symptoms ^[11]. Similarly, data from a cross-sectional study found a median diagnostic delay of eight years for spondyloarthritis, and delayed diagnosis was also associated with worse outcomes and poor treatment responses ^[12].

There have been recent initiatives to develop a more personalized and precision-based approach to chronic pain diagnosis and treatment. For example, one study examined a diagnostic approach that would address specific mechanisms behind “non-specific” chronic low back pain to personalize treatment ^[13].

To localize pain anatomically, a proper musculoskeletal (MSK) physical exam and local anesthetic injections may be utilized as diagnostic tools. However, the MSK physical exam has limited localizing value, and local anesthetic injections are an invasive means of deriving diagnostic information. It is valuable to monitor for changes in the quality of the patient’s pain that may suggest persistent changes in central nervous system (CNS) nociceptors, which may decrease the relevancy of identifying a precipitating peripheral cause of pain.

3. Pain Subclassifications

Neuropathic pain is one example of a condition that has been brought up numerous times as a major epidemiological problem needing systematic classification ^[14]. In 2018, the World Health Organization (WHO) released the first ever systematic classification of chronic pain diagnoses as part of the ICD-11. Given the high global prevalence of chronic pain, affecting over 30% of the world population ^[15], the development of a systematic classification for chronic pain facilitates the collection of thorough epidemiological data. These subclassifications have been used to report health care statistics from January 2022 and onwards. The classification system discussed below is intended to apply to specialized pain management and primary care alike.

When diagnosing chronic pain, it is important to distinguish chronic primary pain from chronic secondary pain syndromes Chronic primary pain is defined by the IASP as pain in one or more anatomical regions that is characterized by significant emotional distress or functional disability, and which is not better explained by an alternative chronic pain subclass ^[16]. Chronic primary pain syndromes include fibromyalgia, complex regional pain syndrome, chronic primary headache, chronic primary visceral pain such as irritable bowel syndrome, and chronic nonspecific low-back pain. These conditions are precluded by chronic pain that can be characterized as a standalone primary diagnosis (Table 1)

Table 1. Chronic primary pain syndromes vs. chronic secondary pain syndromes.

Chronic primary pain syndromes: pain in one or more anatomical regions characterized by significant emotional distress or functional disability	Chronic secondary pain syndromes: pain arising from another health or underlying medical condition
Examples: - Fibromyalgia - Complex regional pain syndrome - Chronic primary headache - Chronic primary visceral pain - Nonspecific lower back pain	Subcategories: - Chronic cancer-related pain - Chronic postsurgical/post-traumatic pain - Chronic neuropathic pain - Chronic headache and orofacial pain - Chronic secondary visceral pain - Chronic secondary musculoskeletal pain

In contrast, chronic secondary pain syndromes arise from another health condition as the underlying cause. In these conditions, pain may have been a symptom of an underlying illness prior to becoming its own autonomous health condition. The diagnosis of chronic secondary pain syndrome may be prompted when the patient’s pain requires its own care and treatment plan, or when the pain persists despite resolution of the initial underlying illness. It is important to exclude patients who have underlying conditions commonly associated with pain, but do not themselves meet criteria for a co-diagnosis of chronic pain.

Chronic secondary pain is further divided into six subcategories, all of which must still meet the minimum 3-month duration for chronic pain. These subcategories include chronic cancer-related pain, chronic postsurgical or post-traumatic pain, chronic neuropathic pain, chronic headache and orofacial pain, chronic secondary visceral pain, and chronic secondary musculoskeletal pain. Chronic cancer-related pain may be caused by cancerous growth or spread or by chemotherapy or radiation treatment. Meanwhile, pain related to surgical intervention for cancer falls under the chronic postsurgical or post-traumatic pain category. Notably, postsurgical pain often stems from a peripheral neuropathic etiology. Therefore, chronic neuropathic pain is a common co-diagnosis. Chronic daily headache is defined by the International Headache Society (IHS) as “15 or more headache episodes per month for at least three months ^[17]”

4. Somatosensory Assessments

Common chronic pain management seeks to initially rule out any treatable causes of the pain, and then to provide the patient with as high a quality of life as possible ^[18]. Somatosensory assessments of pain in a clinical setting often use cutaneous stimuli, such as touch and light pressure, or deep pressure stimuli, such as manually inflated cuffs or instruments for pressure. Most commonly, pain thresholds are evaluated by applying cutaneous and deep pressure stimuli to control sites and the sites of reported pain. Research has suggested the use of mechanical stimuli, such as touch or punctuate pressure, are predictive of pain intensity ^[19].

The current gold standard of chronic pain assessment is based on self-reports of sensory intensity. This can be used via categorical scales, numerical rating scales, visual analog scales, and descriptor scales, though numerical scales are the most used. This method relies on patient recall to define temporal features of pain, i.e., the variability of the pain: whether it is intermittent, constant, or changing in intensity. The recommended numerical rating scale asks patients to rank their pain on a 0–10 scale, with 0 as an indication of no pain and 10 equaling the worst possible pain ^[20].

Current guidelines for assessing somatosensory function in chronically ill patients have been outlined by the German Neuropathic Pain Network (DFNS) ^[21]. These include measures to evaluate for temporal and conditioned pain and are used to explore facilitators and inhibitors of pain. For young children or patients with limited verbal ability, it has been suggested that the use of a Faces Pain Scale may be a more accurate predictor, in which patients are shown pictures of facial expressions depicting pain and asked for the image they identify their pain with ^[22]. Quantitative sensory testing (QST) is another developing assessment that can be used to examine thermal (cold, warmth, etc.) and mechanical thresholds (touch and vibration) to characterize peripheral and central mechanisms of pain.

5. Imaging and Clinical Prediction Models

Neuroimaging, such as MRIs, may also be used to assess chronic pain. The functional MRI (fMRI) measures changes in blood oxygenation levels and is an indirect indicator of brain activity. Resting state fMRIs are conducted to view the brain activity of a patient in chronic pain without additional external stimuli, to provide a baseline of the brain’s functional connectivity ^[23]. This may be compared to the brain’s activity when the chronic pain is exacerbated, specifically seeking alterations in brain networking of resting low oscillatory activity. Other methods of assessing cerebral brain flow for chronic pain include PET and arterial spin labelling⁵³.

Multivariate pattern analysis (MVPA) may additionally be used to compare healthy controls to individuals in pain. This requires patterns of brain activity in control versus chronic pain patients to specify brain structure or activity that may be contributing to pain. Over time, MVPA is anticipated to become a more widely acknowledged diagnostic tool to aid in defining prognoses and tailoring treatment to an individual’s brain activity and structure ^[24].

As the MRI assesses spatial resolution, it may be more accurate to combine neuroimaging with measurements of temporal resolutions, such as the EEG or MEG ^[24]. However, the expense and lack of specificity associated with neuroimaging limits the clinical use of this method, especially when compared to the practicality of self-reports. Further methods of quantifying chronic pain may include genotyping (identifying genetic markers of mechanisms that contribute to pain), pharmacological studies (clinical responses to drugs), and chemical neuroimaging (ligand-based imaging/magnetic resonance spectroscopy). Nonetheless, these methods remain of low clinical utility, as they are both nonspecific and expensive ^[20].

Several risk factors have been attributed to chronic pain, including socio-economic, psychological, clinical, and biological factors. Prior literature concluded that to prevent and reduce the impact of chronic pain, modifiable risk factors (e.g., nutrition, physical activity, and acute pain) need to be addressed ^[25].

6. Management of Chronic Pain

Conservative management of pain is generally the first intervention tried by patients when symptoms of pain first arise, and treatment strategies often include avoidance of triggers for pain, physical therapy, and often non-narcotic analgesics. Due to the multifactorial disease process and various parts of pathophysiology yet still unknown with chronic pain, multiple treatment modalities are needed to produce significant pain relief for patients ^[26]^[27]. A biopsychosocial approach to multidisciplinary pain management can coexist with use of analgesics, interventions, etc. ^[28]. Generally, opioids are less effective for chronic non-cancer pain compared to use on a short-term basis and at low doses used for acute postsurgical pain ^[29]. Besides pharmacological treatment for chronic pain, there have also been studies concluding there is an inverse dose–response association between physical activity and chronic pain ^[30].

Pharmacological treatment of chronic pain conditions primarily associated with nociception include acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs) and other neuroactive drugs for patients with neuropathy or central sensitization. Education, physical exercise, and cognitive behavioral therapy have been shown to be effective for almost any type of pain ^[31]. Neuromodulation techniques for pain management have also been on the rise ^[32]^[33]^[34]^[35]. Local anesthetics have also been used beyond intraoperative anesthesia and analgesia for treatment of both acute and chronic pain conditions ^[36]^[37]. There needs to be a strong therapeutic alliance between clinicians and patients, from diagnosing and classifying chronic pain to correctly imaging, assessing, and ultimately treating the disease.

Antidepressants have also been employed as an off-label treatment for chronic pain conditions such as fibromyalgia, neuropathic pain, and musculoskeletal pain. One meta-analysis ^[38] examining several antidepressants for chronic pain outcomes found duloxetine as the only option with effectiveness as a pain reliever. Medical cannabis is another treatment that has gained more popularity to treat chronic pain more refractory to other pharmacological and interventional methods.

Interventional pain management and sometimes even surgical intervention may be indicated for chronic pain with a lumbar spine etiology. For example, therapeutic epidural injections—caudal, lumbar, interlaminar, and transforaminal—have been utilized to manage chronic lower back pain secondary to disc herniation.

Radiofrequency ablation (RFA) is another interventional procedure using heat to treat chronic lower back pain associated with lumbar facet and sacroiliac joints. One review of eleven RCTs showed evidence for RFA as an effective short-term treatment but less so for the treatment of intervertebral (discogenic) pain ^[39]. There has been a recent interest and growing research into discogenic chronic lower back pain being treated with intraosseous basivertebral nerve (BVN) ablation. BVNs are thought to be responsible for transmitting pain signals from vertebral end plates often associated with discogenic disease ^[40].

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