Ever Wonder Why Some Wounds Hurt and Others Don’t?

Pain is a frequent symptom of patients living with chronic wounds and contributes to suffering and reduced quality of life.9,65,66 Studies have shown that more than 80% of patients with chronic wounds are in constant pain and half of them classify their pain as moderate to severe.1-4 Pain is subjective and can best be described as whatever the patient says it is and exists whenever they says it does.67 In a large prospective study of 758 patients it was found that the more chronic the duration, the higher the reported wound pain (P = 0.022).5 This study also reiterates the importance of early and aggressive pain treatments to avoid the potential spiraling effect of chronic wound pain later on.5,64 In recent years, there has been an increasing awareness of the amount of pain patients with chronic wounds experience.6,7,12

Researchers in 2002 conducted a multinational survey of over thirty-nine thousand wound care practitioners from eleven different countries and found they rated dressing removal as the time of greatest pain.12 Although only limited research has been completed on chronic wound pain, it’s not surprising that most has focused on pain at dressing removal. 6-11 One consistent point stands out in these papers: an agreement that the underlying cause of chronic wound pain is related to inflammation.6,7,11 Despite this, an extensive literature search could not find a clinical pathway for chronic wound pain related to chronic wound inflammation. The purpose of this paper is to present such a pathway and demonstrate that by breaking the chronic wound inflammation cycle, wound pain can be better controlled. Following tissue injury, persistent inflammation triggers a cascade of events that activates local pain receptors. This results in greater sensitivity of the surrounding skin and deeper structures in the wound base. The pain itself can be caused by tissue damage (nociceptive) or nerve damage (neuropathic). The molecular environment of chronic wounds contains elevated levels of inflammatory cytokines and proteases, with low levels of mitogenic activity, and cells that are approaching senescent which fail to respond to growth factors.13,24 Although the inflammatory profile differs in the various types of chronic wounds, this general relationship affects all chronic wounds.13,24,25 When the inflammatory cycle is prolonged, a “vicious cycle” characteristic of all chronic wounds, is created.13 This “vicious cycle” was first describe by Mast and Schultz in 1996 and clearly explain the self-sustaining nature of a prolonged inflammatory phase and its far reaching effects. Their diagrammatic representation of the pathophysiologic characteristic of acute and chronic wounds is an excellent representation of the micro wound environment to date and has been validated by many other researchers. 24,25,26,27,28,29,30,31,32,33,34,35 Once the chronic wound becomes stuck in the inflammatory phase and wound healing is prolonged, pain increases5. As the same chronic wound begins to heal, the micro-wound environment shifts to one that resembles a healing wound and wound pain is reduced; the connection between prolonged inflammation and pain seems clear.5-7,11 Edema remains one of the body’s first responses to inflammation. Chronic edema causes peri-capillary cuffing which starves tissue by reducing the amount of oxygen and nutrients delivered to the wound tissue.39,40 The presence of infection only widens this oxygen debt.41 This hypoxic environment helps to drive the wound deeper into a “vicious cycle” of self perpetuating inflammation as describe by Mast and Schultz.13 Untreated, overtime edema contributes to a shift from hypoxic to ischemic, as fibrin is deposited around the capillary beds forming a fibrin cuff. As capillary beds begin to collapse because of excessive tissue pressure, blood flow becomes sluggish and leukocytes begin to adhere to each other resulting in “plugging” of the capillaries.42,43,44 This results in an ischemic-reperfusion injury.45-56 The lack of available oxygen leads to anaerobic metabolism which reduces concentrations of adenosine triphosphate (ATP) and results in metabolic acidosis. The reduction of ATP facilitates increased lactate with decreasing pH. This “excites” nociceptors and produces activation of pH-sensitive ion channels, resulting in pain.14 Likewise, if there is sufficient oxygen for aerobic metabolism, then the by-product acid is metabolized into carbon monoxide and water, representing the final step of complete metabolism. As a result, pain is reduced or alleviated.15 – 22 This theory may explain why acute wounds have lower levels of associated pain when compared to chronic wounds. It also explains the success Coloplast is having with its ibuprofen-foam in reducing wound pain, as ibuprofen is a non-steroidal anti-inflammatory drug (NSAID).57-62 In 2009 a team of researchers clearly demonstrated that ibuprofen could down regulate proinflammatory cytokines when applied topically, further supporting this theory.63 This theory has also been indirectly supported by researchers using transcutaneous oxygen tensions measurement (TcPO2), who have demonstrated that edema reduces TcPO2 levels: once edema is controlled these levels increase.36,37,38 By breaking the inflammatory phase of healing, chronic wound pain can be controlled.

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