Zyp Czyk's List: Harm from Pain

• Massage
• Balanced Analgesia
• Massage
• Massage
• Relaxation
• Relaxation
• Patient Safety and Quality: An Evidence-Based Handbook for Nurses.
• Chapter 17Improving the Quality of Care Through Pain Assessment and Management

• Background

  At some point in life, virtually everyone experiences some type of pain. Pain is often classified as acute or chronic. Acute pain, such as postoperative pain, subsides as healing takes place. Chronic pain is persistent and is subdivided into cancer-related pain and nonmalignant pain, such as arthritis, low-back pain, and peripheral neuropathy. These authors will draw from the body of knowledge related to chronic pain; however, this chapter will focus on the evidence supporting management of acute pain experienced by hospitalized adults
• nadequately managed pain can lead to adverse physical and psychological patient outcomes for individual patients and their families. Continuous, unrelieved pain activates the pituitary-adrenal axis, which can suppress the immune system and result in postsurgical infection and poor wound healing. Sympathetic activation can have negative effects on the cardiovascular, gastrointestinal, and renal systems, predisposing patients to adverse events such as cardiac ischemia and ileus.
• unrelieved pain reduces patient mobility, resulting in complications such as deep vein thrombosis, pulmonary embolus, and pneumonia.
• Continuous, unrelieved pain also affects the psychological state of the patient and family members. Common psychological responses to pain include anxiety and depression. The inability to escape from pain may create a sense of helplessness and even hopelessness, which may predispose the patient to a more chronic depression. Patients who have experienced inadequate pain management may be reluctant to seek medical care for other health problems
• Importance of Controlling Pain
• Poorly managing pain may put clinicians at risk for legal action. Current standards for pain management, such as the national standards outlined by the Joint Commission (formerly known as the Joint Commission on Accreditation of Healthcare Organizations, JCAHO),⁵ require that pain is promptly addressed and managed.
• Hospitals stand to lose reputation as well as profit if pain is poorly managed. Patient satisfaction with care is strongly tied to their experiences with pain during hospitalization. Evidence indicates that higher levels of pain and depression are linked to poor satisfaction with care in ambulatory settings.⁸ With the advent of transparent health care, report cards for hospitals are becoming more prevalent, and performance on pain management is likely to be one of the indicators reported.

• Undertreatment of Pain

  The undertreatment of pain was first documented in a landmark study by Marks and Sachar in 1973.⁹ These researchers found that 73 percent of hospitalized medical patients had moderate to severe pain. The undertreatment of pain continues. Thirty years later in 2003, Apfelbaum and others² found that 80 percent of surgical patients experienced acute pain after surgery, and 86 percent of those had moderate to extreme pain.
• Patients suffer from pain in many ways. Pain robs patients of their lives. Patients may become depressed or anxious and want to end their lives. Patients are sometimes unable to do many of the things they did without pain, and this state of living in pain affects their relationships with others and sometimes their ability to maintain employment.
• What is often overlooked is that pain has physically harmful effects. It is often actually physiologically unsafe to have pain.¹³ The effects of pain on the endocrine and metabolic system, cardiovascular system, gastrointestinal system, and immune system—and the potential for future pain—are but a few of examples of how unsafe unrelieved pain may be.¹³
• The cardiovascular system responds to stress of pain by activating the sympathetic nervous system, which produces a variety of unwanted effects
• Since the stress response causes an increase in sympathetic nervous system activity, intestinal secretions and smooth muscle sphincter tone increase, and gastric emptying and intestinal motility decrease. This response can cause temporary impairment of gastrointestinal function and increase the risk of ileus.^{13, 15}
• Stress and pain can suppress immune functions, including the natural killer (NK) cells that play a role in preventing tumor growth and controlling metastasis.^{13, 16}
• Harmful Effects of Unrelieved Pain
• Unrelieved acute pain can result in chronic pain at a later date.
• Assessment of Pain
• In a sample of physicians and nurses, Anderson and colleagues²¹ found lack of pain assessment was one of the most problematic barriers to achieving good pain control.
• In the pain history, the nurse identifies the patient’s attitudes, beliefs, level of knowledge, and previous experiences with pain. Expectations of patient and family members for pain control postsurgically will uncover unrealistic expectations that can be addressed before surgery. This comprehensive pain history lays the foundation for the plan for pain management following surgery, which is completed collaboratively by the clinicians (physician and nurse), the patient, and his or her family.
• Pain History

• The pain history should include the following:

  • Significant previous and/or ongoing instances of pain and its effect on the patient
  • Previously used methods for pain control that the patient has found either helpful or unhelpful
  • The patient's attitude toward and use of opioids, anxiolytics, or other medications, including any history of substance abuse
  • The patient's typical coping response for stress or pain, including the presence or absence of psychiatric disorders such as depression, anxiety, or psychosis
  • Family expectations and beliefs concerning pain, stress, and postoperative course
  • Ways the patient describes or shows pain
  • The patient's knowledge of, expectations about, and preferences for pain management methods and for receiving information about pain management²² (

• Current Guidelines

  Many State and professional organizations have developed clinical practice guidelines to direct health care providers in adequate management of acute pain. The 1992 Acute Pain Clinical Practice Guideline²² lays the foundation for the more current guidelines. Listed below is a sample of current guidelines available from the National Guideline Clearing House.

• Research Evidence

  Analgesics, particularly opioids, are the primary treatment for acute pain. It is estimated that up to 90 percent of cancer pain can be adequately managed with analgesics using the World Health Organization (WHO) analgesic ladder.^{33, 34}

• Nondrug Techniques To Manage Pain

  People naturally use many nondrug strategies, such as distraction, imagery, and massage, to alleviate pain. During episodes of acute pain, patients may rely on these previously used and “proven” methods.
• While there are many factors that contribute to poor pain management—lack of assessment and inadequate or inapposite use of analgesics are primary, and modifiable, factors.³
• The objective for postsurgical and procedural pain is to prevent and control pain
• his does not mean that patients will be pain free, a misconception that some patients and families have
• A multimodal approach (balanced analgesia), which includes opioids, nonopioids such as nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant medications such as anticonvulsants, is recommended. (For more detail go to the
• Principle of Analgesic Management of Pain
• Based upon evidence and clinical practice, there are several principles of analgesic management to meet the objective of preventing moderate to severe pain:
• • When continuous pain is anticipated, a fixed-dose schedule (around the clock) should be used.
  • A PRN order of a rapid onset analgesic may be necessary to control activity-related (breakthrough) pain.
  • To ensure opioids are safely administered, begin with a low dose and titrate to comfort.
  • Modification in analgesic administration is based upon assessment of the effect of the previous dose, including change in pain intensity, relief, and side effects experienced.
  • Patients respond differently to various opioid and nonopioid analgesics; therefore if one drug is not providing adequate pain relief, another in the same class may result in better pain control.
  • Assessment of effect should be based upon the onset of action of the drug administered; for example, IV opioids are reassessed in 15–30 minutes, whereas oral opioids and nonopioids are reassessed 45–60 minutes after administration.
• Opioid Analgesics
• The first review³ concluded that patient-controlled analgesia (PCA) and epidural routes of administration were superior to intramuscular (IM) injections when pain intensity and relief were considered.
• The safety of opioids used to control postsurgical pain was examined for hypotension and respiratory depression; observed rates were less than 5 percent for hypotension and less than 1 percent for respiratory depression.
• The most common opioid side effects included 25 percent nausea, 20 percent vomiting, 23.9 percent mild sedation, 2.6 percent excessive sedation, 14.7 percent pruritis, and 23 percent urinary retention
• The use of intravenous PCA was associated with the highest levels of nausea and sedation, whereas epidural analgesia was associated with the highest rate of urinary retention.

• Use of multiple nondrug therapies for pain management

  Introduction to a variety of nondrug techniques may be used to better meet patients’ needs.
• Approximately one in every four patients will experience common opioid side effects; however, the rate of excessive sedation, respiratory depression, and hypotension related to opioids are low in the postsurgical population.
• The essential elements of pain education include telling the patient the following:
• • Preventing and controlling pain is important to your care.
  • There are many interventions available to manage pain; analgesics (opioid and nonopioid) are the most effective in managing acute pain.
  • Some people are afraid of using opioids because of the side effects and risk of addiction. Side effects can be managed effectively with medication. The risk of addiction when using opioids to control acute pain is extremely low.
  • Your responsibility in achieving good pain control is to tell us when you are experiencing pain or when the nature or level of pain changes.
  • Complete pain relief usually is not achievable; however, we will work with you to keep pain at a level that allows you to engage in activities necessary to recover and return home.
• Patient-Nurse Interactions
• While administering analgesics may be the most appropriate way to meet the patient’s needs, the nurse may uncover other factors contributing to discomfort, such as uncomfortable position, thirst, or the need to urinate.
• The use of nondrug therapies is recommended in most pain guidelines; however, the evidence for their consistent benefit in terms of pain intensity, relief, or improved function is weak at best
• • Listening to patient concerns
  • Communicating the desire to help the patient become more comfortable
  • Determining strategies that might achieve more comfor
• Of note, four dimensions (frequent communication, shared goals, shared knowledge, and mutual respect among clinicians) were associated with this improvement in pain control. Thus, this study suggested that communication, goal setting, and patient education contributed to better pain outcome.
• Relaxation
• Reviews on the effectiveness of relaxation for pain relief have arrived at different and often opposite conclusions.^44–46 This is not surprising because of the wide variety of techniques that were used as well as the small number of studies published (11 to 12 in the most recent reviews). The recent randomized clinical trials also contribute to this inconsistency.^{43, 47, 48} Therefore, the current evidence does not support a consistent, predictable effect of relaxation on pain.
• Music
• Sedating or soothing music is instrumental, rhythmic, and 60–80 beats per minute. In much of the research, musical pieces are selected from five types of music identified by Good and colleagues:⁴⁹ synthesizer, harp, piano, orchestral, or slow jazz. The intervention is delivered via audiotape and headphones. The duration is typically 20–30 minutes and may involve a single or multiple exposures.
• Of all the analgesics used in pain control, the most safety issues arise with the use of those referred to as mu opioids, or morphine-like drugs such as morphine, hydromorphone (Dilaudid™), and fentanyl. Clinicians fear causing harm with these analgesics by administering too much and causing life-threatening respiratory depression. Sometimes this fear results in undertreatment of pain.
• Massage
• Massage is defined as the systematic manipulation of soft tissues by manual or mechanical means.⁵⁵ Nurses have used massage—a back rub—to improve circulation, promote comfort, and enhance sleep. More recently investigators have examined hand and foot massage as an alternative to back or body massage.
• Reviews of the massage literature conclude it has a beneficial effect on anxiety and tension, depression, and stress hormones (cortisol and catecholamines).^{57, 58} The evidence on the beneficial effects of massage on reducing pain is positive, but involves few studies, so that firm conclusions cannot be drawn. More recent studies produced inconsistent findings, particularly in terms of the effect of massage on pain control.^{56, 59 62} As with the relaxation and music literature, studies of the effect of massage suffer from methodological problems⁵⁷ that produce unstable or biased results.
• Heat/cold therapy
• Despite the use of heat and cold by nurses, there are few studies investigating the impact on pain or function. A meta-analysis of heat and cold for low-back pain concluded that continued use of heat (over a 5 day period) improved pain intensity and function.
• The application of ice/cold for low-back pain has limited evidence to support it’s use
• Evidence-Based Practice Implications
• The evidence base supporting the use of analgesics to manage acute pain is strong and clear—to date, analgesics, particularly opioids, are effective in controlling acute pain. Undertreatment of acute pain, however, remains prevalent despite the availability of analgesics and guidelines. Undertreatment is attributed to clinician behaviors—lack of adequate pain assessment and inadequate prescription and administration of analgesics—that are modifiable.
• The evidence base for the use of nondrug therapies to manage acute pain requires further development; the current knowledge does not support achieving consistent outcomes from these therapies
• Balanced Analgesia
• Analgesics are usually divided into three categories: (1) nonopioids, which include acetaminophen and NSAIDs; (2) opioids, which include morphine-like drugs; and (3) adjuvant analgesics, which include local anesthetics and anticonvulsants
• Using an analgesic from each one of the three groups, referred to as balanced or multimodal analgesia, may improve the safety of analgesic therapy. When more than one analgesic is used, the same level of pain relief may be achieved with a lower dose of each analgesic. For example, use of a local anesthetic along with an opioid usually allows reduction of the opioid dose needed for adequate pain control.
• Safe Use of Opioids
• Opioid-induced respiratory depression is preceded by an increasing level of sedation. An alert patient will not suddenly succumb to respiratory depression. Consequently, respiratory depression can be prevented by observing sedation levels and decreasing the opioid before respiratory depression occurs.
• Conclusion
• Education about safe pain management will help prevent undertreatment of pain and the resulting harmful effects.
• Use of analgesics, particularly opioids, is the foundation of treatment for most types of pain. Safe use of analgesics is promoted by utilizing a multimodal approach, that is, using more than one type of analgesic to treat the individual’s pain.
• While nondrug techniques pose minimal safety issues, the current evidence does not support that these techniques produce consistent, predictable pain management outcomes.

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• Background

  Chronic non-cancer pain is an increasing problem in health care. This study was initiated by a patient wanting to discover more about the experiences of other patients requiring strong opioid analgesia for such pain.

• Aim

  To determine the attitudes and experiences of patients receiving long-term strong opioid medication for chronic non-cancer pain in primary care.

• Design of study

  Qualitative study using interpretative phenomenological analysis.

• Method

  The study data came from a focus group and 10 individual patient interviews. A patient researcher was involved in the design, conduct, and analysis of the project.

• Results

  The impact of pain affected participants in every aspect of their daily lives. Attitudes to strong opioid medication were both positive and negative. Concerns about starting medication usually centred on fears of addiction, being seen as an addict, or that the patients may have a more serious condition than they had previously thought. However, these fears were tempered by an appreciation of the benefits that strong opioids brought in terms of pain relief and consequent gains in a nearer-to-normal existence. The data did not produce any evidence of addictive behaviour or of tolerance despite these initial fears. Patients adopted a trade off approach, balancing pain relief with medication side effects, accepting more pain for a reduction in sedation and nausea. All patients described coping strategies they developed themselves and learned from outside influences, such as pain clinic courses and support from the GP. There was realism that total pain relief was not possible, but that a balance could be struck.

• Conclusion

  Chronic non-cancer pain is associated with high levels of distress and psychosocial impairment. Patients in this study appreciated the benefits of strong opioid medication, having come to terms with fears of addiction and learned coping strategies. These findings should encourage GPs to consider strong opioid medication for patients with severe chronic pain in line with published evidence-based guidelines.
• Chronic pain is a significant health burden in our society. Although guidelines exist for the use of strong opioid medication, fears remain among patients and doctors about long-term use. This study shows that these medications can give effective analgesic benefits and patients adopted strategies for trade-off between pain control and side effects of medication. Coping strategies and a positive GP-patient relationship were also regarded as important.
• Chronic pain had made a profound impact on the lives of all the patients in the study and their partners and families. All participants consistently reported social isolation, limitations in activities of daily living, loss of a previous lifestyle, and perceived stigma. The pain made them miserable and unsociable and they were constantly frustrated by the things that they could not do and that others had to do for them

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• there is a functional reorganization of the cerebral cortex in chronic pain, for example, FMS, IBS, and chronic back pain, but also there is actual anatomic decrease in the gray matter of various regions of the brain.
• In FMS, a reduction in gray matter has been demonstrated in left parahippocampal gyrus, cingulated gyrus, insula, and medial frontal cortex.
• CSS diseases are based on a neurochemical pathology, and they are not psychological or psychiatric illnesses.
• Multiple symptoms in these patients have a demonstrable pathophysiological basis and do not represent somatization.

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• Changes in the formulations of OxyContin and Opana, making them less subject to misuse, ironically have former abusers of those drugs turning to deadly heroin, according to reports in the New England Journal of Medicine and USA Today. Meanwhile, as another unintended consequence, some patients with chronic pain say the newly formulated opioids do not work for them as well as before
• “The most unexpected, and probably detrimental, effect of the abuse-deterrent formulation was that it contributed to a huge surge in the use of heroin,” Cicero and colleagues observed. “We’re now seeing reports from across the country of large quantities of heroin appearing in suburbs and rural areas. Unable to use OxyContin easily, which was a very popular drug in suburban and rural areas, drug abusers who prefer snorting or IV drug administration now have shifted either to more potent opioids, if they can find them, or to heroin.”

• Jargon often influences attitudes and impedes communication between healthcare providers and patients, which can impact the quality of pain care. Nowhere is this more apparent than in the use of “narcotics” rather than “opioids” in reference to pain relievers, and the results of a recently reported study comparing patients’ understandings of the two terms were both surprising and disturbing.
• In the study — conducted by Lorraine Wallace, PhD, of Ohio State University, and colleagues — a convenience sample of 188 English-speaking women who were visiting a primary care clinic completed a 4-question survey. The women were generally healthy, aged 21 to 45 years, and 81% were Caucasian. Each participant was randomly assigned to either a survey version using the term “opioid” or a second version using “narcotic” as follows [Wallace et al. 2012]:
• • What is [an/a opioid/narcotic]?
    
    
  • Give an example of [an/a opioid/narcotic]?
    
    
  • Why does someone take [an/a opioid/narcotic]?
    
    
  • What happens when someone takes [an/a opioid/narcotic] for a long time?
• the researchers report that more than half of participants (56%) responded “don’t know” to all 4 questions when “opioid” was used, while just 3% responded “don’t know” to all 4 questions using the term “narcotic” (P < 0.01). Most of the women were unfamiliar with the term opioid (76%) and did not know why someone would take an opioid (69%). Whereas, about two-thirds of respondents were able to give an example of a narcotic (64%) and, surprisingly, most of them specified consequences of long-term narcotic use as being addiction-related (63%).
• Wallace and colleagues also note that their findings were almost identical to an earlier survey among a predominantly male veteran population (N=100), in which 78% expressed fear of adverse outcomes from long-term “narcotic” use, with 66% citing addiction as a consequence [Mangione and Crowley-Matoka, 2008].
• terminology could impact patient care, with “opioid” making treatment seem more medical, while “narcotic” insinuates furtive or adverse underpinnings. However, they also concede that using “opioid” — which is the more accurate medical term to describe these analgesics — without clarification and patient education may only lead to confusion.
• Briefly, dictionaries typically define “narcotic” as a drug that in moderate doses dulls the senses, relieves pain, and may induce sleep, but in excess causes stupor, coma, convulsions, or death. Often, narcotic drugs are described as capable of producing addiction. At one time, “narcotic” pertained only to opium or its derivatives, but the term was usurped by government agencies dating back more than a century ago to include cocaine, as well as illicit forms of drugs in the sedative, stimulant, and hallucinogen classes (interestingly, although cannabis, or marijuana, was traditionally demonized it was never included in the narcotic category). Thus, “narcotic” has legal and regulatory implications extending well beyond the medical aspects of these drug classes, particularly opioids.
• “Opioids” is an umbrella term that incorporates opiates, which includes drugs derived directly from opium (eg, codeine, morphine), as well as a range of synthetic or semisynthetic morphine-like drugs. Unfortunately, many uninformed writers and speakers often use the term “opiate” when they actually are referring to the broader family of opioids, but this might be viewed as a relatively minor affront.
• By far, the greater transgression is using “narcotic” in reference to legitimate, prescribed opioid analgesics. In common lore, and as supported by the above research studies, the term “narcotic” has become strongly associated with both legal and illicit drugs that can be harmful and/or addictive. Thus, the term not only elicits fear among patients, but it also raises a spectre of evil-doing among healthcare professionals who prescribe “narcotic drugs” for these patients.
• These perceptions are furthered by news media that refer to “narcotics” in stories of abuse, misuse, addiction, and diversion of prescription opioid analgesics. Worse yet, they often describe these drugs as “narcotic painkillers,” rather than pain relievers, in headline news about overdoses and deaths — fostering a distorted perception of these drugs as being excessively unsafe and lethal. Thus, intentionally or not, news reporters are fueling public fears and outrage against a class of medications that serve vital needs among millions of persons with pain.
• The automatic association of “narcotics” with addiction also is of concern. Roughly two-thirds of respondents in both studies cited above associated narcotics with addiction — as a consequence of long-term use — compared with only a small minority of those asked about “opioid” effects.
• Most likely, patients fears of “narcotic addiction” being commonplace — a belief that also has been adopted by some healthcare professionals — are an exaggeration driven by sensational news reports, biased government declarations, and poor-quality research evidence.
• Finally, it must be recognized that these problems are not exclusive to the U.S. The term “narcotic” still lingers at the World Health Organization (WHO) in the names of committees and titles of papers dealing with legitimate opioid agents, and in documents from the International Association for the Study of Pain (IASP), to name just two organizations. In many countries the language surrounding opioid analgesics is pejorative: for example, in Austria patients with pain might be given opioid-prescription forms called Suchgiftrezepte, meaning “addictive poison prescription forms”; in Germany, opioid analgesics are referred to as Betäubungsmittel, which translates as “the means to knock you out”
• REFERENCES:
  > Mangione MP, Crowley-Matoka M. Improving Pain Management Communication: How Patients Understand the Terms “Opioid” and “Narcotic.” J Gen Int Med. 2008;23(9):1336-1338 [abstract here].
  > Wallace LS, Keenum AJ, AbdurRaqeeb O, et al. Terminology Matters: Patient Understanding of “Opioids” and “Narcotics”. Pain Practice. 2012(Jun 4); online ahead of print [abstract here].

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• With pharmaceuticals becoming increasingly accessible, poisoning and overdose have become rising concerns in the United States and throughout the world, particularly involving opioid analgesics. Now, a newly published study from the University of Rochester Medical Center reports that nonopioid analgesics and psychotropic agents are more likely to be associated with drug poisoning overdose than opioid analgesics [Wiegand et al. 2012].

• Despite the limitations, data in this report suggests several points for further consideration:

  • An unbalanced focus on opioid analgesic harms neglects other medications, as well as many illicit substances, that have greater or comparable risk for misuse, abuse, and overdose. In particular, nonopioid analgesics confer a 24% greater risk of poisoning and overdose than opioids.
    
    
  • There is an implication that a shift from opioids to other analgesics, as well as adjunctive medications, for treating pain may incur significant harms in persons with pain. The high rate of acetaminophen involvement in poisonings and deaths seems particularly troublesome.
    
    
  • Intentional self-harm (suicide attempt) using pharmaceuticals, representing more than a third of emergency department cases, is of great concern; although it is not known if this relates more to mental health issues or the undertreatment of pain.
    
    
  • Increases in the use of designer psychoactive drugs (eg, bath salts, synthetic cannabinoids), as well as the ongoing presence of drugs like heroin, suggest that substance abuse problems in the population continue to rage out of control — and prescription opioids are only one part of a much larger scenario.

• when chronic pain is unexplained by a diagnosis of some severe biopathology patients often face significant obstacles to being taken seriously by their families, friends, and healthcare providers.
• medical evidence for the pain superseded all other information when judging the genuineness of pain and consequent feelings of sympathy or helpfulness toward the patient
• Therefore, there are still unanswered questions about how the qualities of patients and those interacting with them, as well as available information about patient medical condition and/or psychosocial influences, affect judgments when it comes to pain assessment, sympathy, and helping behavior.

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• Researchers found that in a healthy brain all the regions exist in a state of equilibrium. When one region is active, the others quiet down. But in people with chronic pain, a front region of the cortex mostly associated with emotion "never shuts up," said Dante Chialvo, lead author and associate research professor of physiology at the Feinberg School. "The areas that are affected fail to deactivate when they should."

   

  They are stuck on full throttle, wearing out neurons and altering their connections to each other.
• This is the first demonstration of brain disturbances in chronic pain patients not directly related to the sensation of pain.
• This constant firing of neurons in these regions of the brain could cause permanent damage,
• Chialvo said. "We know when neurons fire too much they may change their connections with other neurons and or even die because they can't sustain high activity for so long,
• This continuous dysfunction in the equilibrium of the brain can change the wiring forever and could hurt the brain."

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• Based largely on recent advances in neuroimaging and neurophysiology, we are beginning to understand that the experience of pain is a multifaceted process affected by somatosensory, emotional, cognitive, and genetic factors—as well as by structural changes in the brain.¹ Chronic pain provokes changes in the central nervous system (CNS) that modify the sensory, emotional, and modulatory circuits that normally inhibit pain.² A clear distinction exists between the effects of acute versus chronic pain on the brain, with chronic pain provoking structural changes in multiple regions of the brain that are involved in cognitive and emotional pain processing.^3,4 These changes increase the risk of altered cognitive and emotional states characterized by fear, anxiety, or depression.²
• he brain’s ability to reorganize in response to chronic pain is characterized by functional, structural, and chemical changes.² Notably, it has been shown that specific areas of the brain, known as the pain matrix, are activated in response to pain. The pain matrix is thought to include the primary (S1) and secondary (S2) somatosensory cortices, insula, anterior cingulate cortex (ACC), amygdala, prefrontal cortex, thalamus, basal ganglia, and cerebellum.^3,4 The insula, S1, S2, and lateral thalamus are involved in the sensory-discriminative aspect of pain processing, while the ACC plays a role in the perception of pain as an unpleasant event.³
• Correlations between changes in gray matter and the duration or severity of pain have also been reported. For example, greater decreases in gray matter have been associated with longer duration of pain.^3,4 On the other hand, increased gray matter has been identified in the ACC, dorsolateral prefrontal cortex, amygdala, and brain stem following effective treatment to relieve chronic pain.³

• Published: 04/16/2013

  References: 

  1. Borsook D, Sava S, Becerra L. The pain imaging revolution: advancing pain into the 21st century. Neuroscientist. 2010;16:171-185.
  2. Borsook D. A future without chronic pain: neuroscience and clinical research. Cerebrum. 2012 May/June. [Epub 2012 Jun 27]
  3. Henry DE, Chiodo AE, Yang W. Central nervous system reorganization in a variety of chronic pain states: a review. PM R. 2011;3:1116-1125.
  4. Schweinhardt P, Bushnell MC. Pain imaging in health and disease—how far have we come? J Clin Invest. 2010;120:3788-3797.

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• Overall, the quality of life of patients with chronic pain is significantly diminished due, in part, to physical and psychological comorbidities, as well as negative effects on social relationships, work, life enjoyment, and the ability to perform usual daily activities.^5,8,9 Chronic pain is associated with higher rates of depression, suicidal thoughts, and suicide attempts, with the prevalence of psychological disorders (such as depression, anxiety, personality disorders) ranging from 33% to 46% compared with 10% of individuals unaffected by chronic pain.⁸ Cognitive impairments, including memory and attention deficits, are evident in as many as two-thirds of patients with chronic pain, while sexual dysfunction is reported by 54% to 63% of patients.⁸ Sleep disorders are a common complaint, estimated to affect 50% to 89% of patients, with the degree of disturbance positively correlated with pain severity.^8,9 Rates of hypertension are also higher among individuals with chronic pain, potentially due to alterations in the overlap between pain pathways and cardiovascular function.⁸
• In addition to these physical and psychosocial effects, chronic pain imposes a significant economic burden. Total annual direct medical costs range from $560 to $635 billion in 2010 dollars, while estimated costs associated with lost productivity are $299 to $335 billion.¹⁰ Notably, the annual expenditures associated with chronic pain exceed those for cardiovascular disease; cancer; injury and poisoning; endocrine, nutritional, and metabolic diseases; digestive disorders; and respiratory conditions.¹⁰

  • $500 Billion in medical costs
    $300 Billion in lost productivity
• Early intervention is essential to prevent or delay the onset of long-term complications and improve the physical and psychological sequelae associated with chronic pain.⁸
• Despite the diversity of treatments for chronic pain, the overall efficacy of treatment is disappointing, with an average pain reduction of approximately 30% in about one-half of treated patients.² Notably, pain reduction does not always result in improved physical and emotional functioning and enhanced quality of life.² Treatment priorities should emphasize optimal symptom relief, with most patients requiring individualized therapeutic regimens based on multidisciplinary combinations of treatment modalities in order to achieve clinically acceptable outcomes.^2,11

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• The case of Dominic Boivin, a Calgary teen who took his life after four years of struggling with constant, and mysterious, body-wide pain. The ILC Dominic Boivin Fund was set up to raise awareness and funds to help bridge the gaps of chronic pain and its associated mental health in children and youths through a national peer support network
• A 16-year-old Burlington teen who attempted suicide because of underdiagnosed chronic pain. The teen and their family met with a geneticist at McMaster Hospital working with the ILC and its DDD program and they discovered that other members in the family had confirmed diagnoses of EDS Joint Hypermobility. The family has since connected with several other families experiencing similar situations through ILC’s peer support network

• Our results delineate for the first time a transcriptomic signature in the prefrontal  cortex resulting from peripheral injury six months prior. Interestingly, both coding  and non-coding transcripts are altered.
• Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex
• Peripheral nerve injury can have long-term consequences including pain-related manifestations,  such as hypersensitivity to cutaneous stimuli, as well as affective and cognitive  disturbances, suggesting the involvement of supraspinal mechanisms. Changes in brain  structure and cortical function associated with many chronic pain conditions have  been reported in the prefrontal cortex (PFC). The PFC is implicated in pain-related  co-morbidities such as depression, anxiety and impaired emotional decision-making  ability. We recently reported that this region is subject to significant epigenetic  reprogramming following peripheral nerve injury, and normalization of pain-related  structural, functional and epigenetic abnormalities in the PFC are all associated  with effective pain reduction.
• hypothesis that peripheral nerve injury triggers persistent long-lasting  changes in gene expression in the PFC, which alter functional gene networks, thus  providing a possible explanation for chronic pain associated behaviors.

• Genes involved in chronic injury and altered neuronal growth and proliferation in  the PFC 

   
• Significantly altered biological processes included neurological disease, skeletal  muscular disorders, behavior, and psychological disorders. Several of the changes  detected by RNAseq were validated by RT-QPCR and included transcripts with known roles  in chronic pain and/or neuronal plasticity including the NMDA receptor (glutamate  receptor, ionotropic, NMDA; grin1), neurite outgrowth (roundabout 3; robo3), gliosis (glial fibrillary acidic protein; gfap), vesicular release (synaptotagmin 2; syt2), and neuronal excitability (voltage-gated sodium channel, type I; scn1a).

• Results

   

   

  Peripheral injury is accompanied by behavioral signs of neuropathic pain six months  post-injury 
• Mutations in sodium channels have been previously implicated in pain and in the modulation  of neuropathic and inflammatory pain
• Peripheral injury is accompanied transcriptomic changes in the prefrontal cortex six  months post-injury
• This is the first demonstration of long-term overexpression of scn1a in the prefrontal cortex following peripheral injury.
• One of the functional gene pathways that is highly enriched by genes that are differentially  expressed six months after nerve injury is the pathway involved in nervous system  development and functions
• Discussion
• Molecular transport and neurological disease
• Chronic pain changes the brain at various levels: changes in cortical grey matter  [33,34], white matter [35], and overall cortical excitability [36] have all been reported
• Nervous system development and function

• Conclusions

   

   

  We demonstrate broad changes in gene expression in the mouse prefrontal cortex six  months after peripheral nerve injury, illustrating a long-term impact of a peripheral  injury on brain genome function

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• Chronic pain has an impact on psychological and social factors. It is known that stress influences physiological and behavioral changes and affects several neurotransmitter and hormonal systems. It is also known that corticosterone is increased by stress.