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Evidence-based approach to manage persistent wound-related pain

Woo, Kevin Y.a,b; Abbott, Laura K.a; Librach, Lawrencec,d

Current Opinion in Supportive and Palliative Care: March 2013 - Volume 7 - Issue 1 - p 86–94
doi: 10.1097/SPC.0b013e32835d7ed2
WOUND MANAGEMENT IN ADVANCED ILLNESS: Edited by Vincent Maida
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Purpose of review Pain is a significant concern in people with chronic wounds. A systematized approach is recommended for the management of wound-associated pain with the objectives to address pain relief, increase function, and restore overall quality of life.

Recent findings Combinations of pharmacological agents are often recommended based on varying degree of pain severity, coexisting nociceptive and neuropathic pain, and chronic inflammation related to wound-associated pain. Topical agents including morphine, tricyclic antidepressants (e.g., amitriptyline), nonsteroidal anti-inflammatory drugs (NSAIDs), capsaicin, ketamine, and lidocaine/prilocaine provide pain relief with minimal side effects. Mindful dressing selection to minimize trauma, handle excess fluid, and prevent periwound skin damage has been shown to reduce persistent wound pain. To avoid nocebo hyperalgesia, it is important to address emotions, anticipation or negative expectation of discomfort.

Summary Pain is a complex biopsychosocial phenomenon that requires multiple pharmacological and nonpharmacological management approach.

aSchool of Nursing, Queen's University, Kingston

bWest Park Health Centre

cTemmy Latner Centre for Palliative Care, Mount Sinai Hospital

dUniversity of Toronto, Toronto, Ontario, Canada

Correspondence to Kevin Y. Woo, School of Nursing, Queen's University, 92 Barrie Street, Kingston, Ontario K7L 3N6, Canada. Tel: +1 613 533 6000x74747; fax: +1 613 533 6770; e-mail: kevin.woo@queensu.ca

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INTRODUCTION

Pain is a common experience in people with chronic wounds. Chronic and persistent pain can have a significant impact on various aspects of everyday life, including physical activity, sleep, social functioning, and erodes individuals’ quality of life [1,2]. Studies of patients with various chronic wound types validate the pervasiveness of pain that is described as intense, unrelenting, distressing, and is often exacerbated at dressing change [3]. Even long after the ulcers are healed, people continue to conjure up vivid descriptions of the pain experiences [4]. Among all the symptoms, pain has been described as the worst part of living with chronic wounds constituting significant level of stress [5▪]. Optimal pain management must be incorporated as an integral part of comprehensive wound management in order to improve quality of life.

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A SYSTEMATIC APPROACH TO WOUND-RELATED PAIN

Pain is a complex biopsychosocial phenomenon; the term ‘pain neuromatrix’ has been used to connote the intricate interactions and integration among a number of pain processing networks [6]. Despite seemingly comparable levels of pain intensity, people with pain experience varying degrees of physical limitations, emotional distress, and suffering [7]. According to the integrated wound-related pain model in Fig. 1, chronic pain, also referred as background, baseline, or persistent pain, is related to the underlying wound pathologies. In contrast, episodic pain is synonymous with intermittent or breakthrough pain that is exacerbated by procedures. Effective management of pain necessitates a systematized approach that integrates both pharmacological and nonpharmacological strategies. Pharmacological therapies may include a combination of agents that target nociceptive and/or neuropathic pain. Although systemic medications are preferred for immediate relieve of pain, topical analgesics have been demonstrated to be a viable option with minimal side effects. Recognizing that pain is often elicited by trauma and tissue damage, nonpharmacological interventions focus on mitigating and preventing mechanical forces (e.g., pressure, friction, and shear), chemical irritation, vascular damage (e.g., venous hypertension and arterial insufficiency), and excessive inflammation [8].

FIGURE 1

FIGURE 1

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PHARMACOLOGICAL STRATEGIES FOR PERSISTENT WOUND-RELATED PAIN

A person-oriented and multifaceted approach (Table 1) is recommended for the management of wound-related pain with the objectives to address pain relief, increase function, and restore overall quality of life [9]. Pharmacotherapy continues to be the mainstay for pain management. Appropriate agents are selected based on severity and specific types of pain. Nociceptive pain incurred by tissue damage activating pain receptors in the muscle, bone, joints and ligaments (somatic pain) or in the viscera, and peritoneum (visceral pain). Pain of nociceptive origin is often described as sharp, dull, aching, throbbing, or gnawing. The World Health Organization's analgesic ladder [10] proposes that treatment of mild (1–3 out of 10) to moderate (4–6 out of 10) nociceptive pain should begin with a weak opioid (such as codeine or tramadol) with or without the addition of acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) [11,12]. In order to control more severe (>6 out of 10) and refractory pain, the treatment should include strong opioid analgesics, such as morphine, hydromorphone, oxycodone, fentanyl, and buprenorphine that can be administered by a number of routes: oral, rectal, subcutaneous, intravenous, transdermal, and neuraxial [13▪]. In addition, a fourth step has been added to incorporate neurosurgical procedures, such as brain stimulator and other invasive techniques, such as nerve blocks and neurolysis (e.g., phenolization, alcoholization, thermocoagulation, and radiofrequency) for more recalcitrant pain [14].

Table 1

Table 1

Box 1

Box 1

Neuropathic pain may coexist with nociceptive pain, caused by injury and sensitization of the peripheral or central nervous system. Following repeated insult, excessive and prolonged inflammation can lead to spontaneous ‘wind-up’ pain or exaggerated or prolonged painful responses to normally painful stimuli (hyperalgesia) and even nonpainful stimuli (allodynia) [15]. Mechanisms for central and peripheral pain sensitization is complex, involving the remodelling of synaptic contacts between the neurons in the spinal dorsal horn circuitry (neuronal plasticity) and the increased activity of inflammatory substance P and glutamate on receptors for neurokinin 1 (NK1) and N-methyl-D-aspartic acid (NMDA) [15,16]. In a chronic wound environment, analysis of wound fluid corroborates a superfluous and prolonged inflammatory response as indicated by high levels of cytokines (e.g. TNF-α, IL-1), proteases, and matric metalloproteinases (MMPs) [17]. Upregulation of inflammatory mediators have been implicated in a number of chronic pain syndromes by causing damage to nerve fibers and altering the central signalling pathways [18,19▪]. Clinically, neuropathic pain is mostly described as burning, stabbing, sharp, and other sensations that resemble electrical shocks and pin pricks [20]. Despite the commonly held belief that most patients with diabetic foot ulcers do not experience pain due to loss of protective sensation, up to 50% of patients experienced varying degrees of painful symptoms at rest and approximately 40% experienced moderate-to-extreme neuropathic pain [21▪]. Management of neuropathic pain or related symptoms may require the addition of adjuvant treatments [22,23]. Three classes of medications are recommended as first-line treatments for neuropathic pain: antidepressants with both norepinephrine and serotonin reuptake inhibition [e.g., tricyclic antidepressants (TCAs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)], calcium channel α2δ ligands (e.g., gabapentin, pregabalin), and topical lidocaine (lidocaine patch 5%) [24,25].

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HOW TO USE ANALGESICS

Whether the pain is of nociceptive or neuropathic origin, selection of appropriate pharmaceuticals should always take into account the characteristics of the drug (e.g., onset, duration, available routes of administration, dosing intervals, side effects) (Table 2) and individual factors (e.g., age, coexisting diseases, and other over-the-counter or herbal medications) [22,23,26]. As a general rule of thumb, analgesics should be taken at regular intervals until pain is adequately relieved. Whenever possible, the oral route of medication administration is preferred. It takes five half-lives of an analgesic agent to reach a steady state; after a titration period with short-acting preparations to estimate the required dosing for managing continuous stable pain, controlled release medications should be considered to facilitate around-the-clock dosing, especially at night. Nonetheless, short-acting medications should still be made available for occasional breakthrough pain. In some cases, it may be necessary to consider the use of two or more drugs from different classes. Their complementary mechanisms of action may provide greater pain relief with less toxicity and lower doses of each drug. Emerging evidence also supports frequent rotation of different medication or administration routes to achieve improved analgesic response [27]. For the elderly population, it is advisable to ‘start low and go slow’ in order to circumvent untoward adverse effects (see common side effects of analgesics in Table 2). Common side effects, such as constipation, nausea, confusion, and drowsiness, should be monitored and managed appropriately. However, if the pain is (anticipated to be) severe pain, conscious sedation – the combination of sedatives and potent opioids, such as sublingual fentanyl or sufentanil (approximately 100 times more potent than morphine) and ketamine – may warrant consideration. In resistant cases, options may include general anesthesia, local neural blockade, spinal analgesia, or the use of mixed nitrous oxide and oxygen [26–28]. Risks, neurotoxicity, and other untoward side effects substantially increase at high doses of opioid. It is recommended that total daily dose of opioid should not exceed 120–200 mg of oral morphine equivalent dose (MED) per day. Referrals to specialized pain centers should be considered for people who are at risk for addiction especially if they have a history of substance abuse and psychiatric disorders.

Table 2-a

Table 2-a

Table 2-b

Table 2-b

Topical agents play a critical role in alleviating wound-related pain. Slow-release ibuprofen foam dressings have demonstrated reduction in persistent wound pain between dressing changes and temporary pain on dressing removal [29]. The topical use of morphine, tricyclic antidepressants (e.g., amitriptyline), NSAIDs, capsaicin, ketamine, and lidocaine/prilocaine has demonstrated effectiveness for pain relief [30▪,31]. However, the lack of pharmacokinetic data precludes the routine clinical use of these compounds at this time. There are many advantages to using local rather than systemic treatment. The active agent is delivered directly to the affected area, bypassing the systemic circulation, and the dose needed for pain reduction is lower, minimizing the risk of side effects.

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NONPHARMACOLOGICAL MANAGEMENT OF WOUND-RELATED PAIN

Wound-related pain is often exacerbated with dressing changes that can persist for a long time (in some cases over 6 h) [32]. Dressing materials adhere to the fragile wound surface due to the glue-like nature of dehydrated or crusted exudate requiring high peel force for removal. In addition, the granulation tissue and capillary loops may grow into the contact layer, especially with gauze dressings and with the use of negative pressure wound therapies, rendering mechanical trauma upon removal [3]. According to a review of dressings and topical agents for post surgical wounds and healing by secondary intention, patients experienced more pain with gauze than any other advanced moisture balance dressings including foam, alginate, and hydrocolloid dressings [33▪]. Ironically, gauze continued to be one of the most commonly used dressing in clinical practice. Careful selection of dressings with an atraumatic and nonadherent wound contact layer, such as silicone, has been documented to limit skin damage/trauma with dressing removal and to minimize pain at dressing changes [34]. Silicone coatings consist of chains of hydrophobic polymers with alternate molecules of silicone and oxygen. As compared with other adhesives, the silicone coatings produce a lower surface tension combined with a more extensive contact interface. Silicone-coated dressings adhere to intact dry skin but unlike traditional adhesives, they do not adhere to a moist wound bed. In a comparative study, Matsumara et al.[35▪] evaluated eight commonly used wound-care products with adhesives (soft silicon, hydrocolloid, polyurethane, and acrylic adhesives) and their potential effect on the epidermis in 10 normal volunteers. Dressings that incorporated soft silicone technology were less likely to cause skin stripping and removal of stratum corneum than other tested material.

Wound-related pain may extend beyond the wound margins to periwound skin. When drainage volume exceeds the fluid handling capacity of dressing material, enzyme rich and caustic exudate may spill over to wound margins causing maceration or tissue erosion and pain [36]. Maceration of the periwound skin typically presents as white, wrinkled soggy tissue at the wound edge. In a crossover, randomized, controlled trial, patients with wound margin maceration and skin damage were prone to experience increased pain even before dressing changes [37]. To contain and remove excess exudate from the wound, a plethora of absorbent dressings have been developed. Based on the absorbency, major categories of dressings include foams, alginates and hydrofibers. Selecting the right dressing and size to absorb the exudate from the wound and the appropriate frequency of dressing change is crucial to optimize persistent wound-related pain (see Fig. 2).

FIGURE 2

FIGURE 2

Some sealants, barriers, and protectants, such as wipes, sprays, gels, and liquid roll-ons, are designed to protect the periwound skin from causative wound exudate and trauma induced by adhesives (Table 3).

Table 3

Table 3

Increased painful symptoms have been linked to wound infection and warrant further assessment. In the presence of unexpected pain or tenderness, clinicians should be suspicious of wound infection. According to a systematic review, Reddy et al.[38] validated that increased pain (likelihood ratio range, 11–20) is an indicator for chronic wound infection. Based on literature review and previous studies, the UPPER and LOWER wound infection checklist was developed incorporating a total of 10 signs and symptoms (Table 4) that are associated with critical colonization (upper compartment) and deep infection (lower compartment). The list of criteria to evaluate wound infection has been validated in previous studies [39,40]. There is no single individual sign or symptom that could accurately confirm the diagnosis of wound infection but a combination of two or three of these possible signs should be sought for the diagnosis in each level. By collating three clinical signs, the sensitivity and specificity for signs associated with critical colonization were reported as 73.3 and 80.5%, respectively [41]. To reduce superficial and localized bacterial burden in chronic wounds, topical antimicrobial dressings (e.g., silver, iodine, honey, and polyhexamethylene biguanide) have been demonstrated to be effective [42].

Table 4

Table 4

Pain is an emotional experience that can be amplified by anticipation or negative expectation of discomfort; also known as nocebo hyperalgesia [8,43]. In fact, the perception of pain is amplified by individual's expectation of pain even when the stimuli are relatively innocuous. In a study of 96 patients with chronic wounds, Woo [44] reported that patients who experienced high levels of anxiety, also reported high levels of anticipatory pain, leading to high levels of pain at dressing change. The result is a vicious cycle of pain, stress/anxiety, and worsening of pain. In responding to a web-based survey, healthcare practitioners (n = 908) acknowledged that mental health concerns are common in people with chronic wounds [45]. Over 60% of the respondents indicated that between 25 and 50% of people with chronic wounds suffer from mental disorders. Among all the symptoms, anxiety was rated the most common (81.5%). Anxiolytic agents and sedatives should be considered as part of the pain management toolkit to mitigate pain-related anxiety. In addition to pain, clinicians should pay attention to other sources of anxiety that may be associated with stalled wound healing, fear of amputation, body disfigurement, repulsive odour, social isolation, debility, and disruption of daily activities [46]. Fear of addiction and adverse effects have prevented patients/residents from taking regular analgesics. In a pilot study, chronic wound patients described dressing change pain as being more manageable after receiving educational information [47▪]. Pain-related education is a necessary step in effecting change in pain management by debunking common misconceptions and myths that may obstruct effective pain management. Cognitive therapy that aims at altering anxiety by modifying attitudes, beliefs, and expectations by exploring the meaning and interpretation of pain concerns has been successful in the management of pain [48]. This may involve distraction techniques, imagery, relaxation, or altering the significance of the pain to an individual. Patients can learn to envision pain as less threatening and unpleasant through positive imagery by imagining pain disappearing or by conjuring a mental picture of a place that evokes feelings and memories of comfort, safety, and relaxation [49]. Emerging evidence suggests the importance of peer support can lead to improved outcomes in pain, healing, and quality of life [50].

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CONCLUSION

Pain is a common concern and affects quality of life in people with chronic wounds. It is imperative to approach wound-related pain by first identifying the triggers related to wound pathologies or procedures, followed by evaluating the number of neurobiopsychosocial factors that may affect the pain experience. A variety of approaches drawing on expertise from interprofessional teams is crucial to optimize pain management.

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Acknowledgements

None.

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Conflicts of interest

None of the authors have any conflicts of interest to declare.

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REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest

Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 123–124).

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REFERENCES

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Keywords:

nocebo; pain management; persistent wound-related pain

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