When patients present with chronic pain, it is crucial for wound clinicians to use a multifaceted approach to pain management. These authors address pain management techniques that include opioids, non-opioid pharmacologics, targeted interventional therapies, and complementary and alternative medicine.
On a scale of 0 to 10, please tell me, how bad is your pain?” is a commonly asked question that clinicians ask their patients. However, what is truly the best way to manage a subjective feeling, such as pain, in patients who experience it?
Pain is often mismanaged in patients because it’s impossible to measure accurately and consistently across various patient populations. To this day, clinicians face difficulty when it comes to pain treatment because they lack sufficient education in the approach, examination, and management of pain. Patients with chronic wounds are particularly difficult to treat because of the range in types of pain these patients may experience. Therefore, as clinicians begin to treat pain, it’s important to understand the pathogenesis of the pain as this will drive the best treatment choice.
Pain is transmitted through peripheral and central mechanisms in the nervous system, as well as modulation of the signal. In the context of chronic wounds, peripheral mechanisms play a significant role in pain experienced by patients. Nociceptive pain, secondary to tissue damage, is commonly experienced by patients with acute and chronic wounds; it is often described as sharp or stabbing in nature and may be persistent because of constant nociceptor stimulation in the area of tissue damage. Neuropathic pain may also be experienced by patients with chronic wounds, specifically those with diabetic foot ulcers (DFUs).
Often described as a burning, tingling, or shooting sensation, neuropathic pain is a common complication of diabetes, and it can be difficult to control. Finally, should a chronic wound become infected, then wound-related bacteria can release mediators of inflammation. This inflammatory response increases the sensitivity of pain receptors, which may increase the overall perception of pain in these patient populations.
From the discussion above, patients with chronic wounds may experience pain from a variety of etiologies. Therefore, in order to manage pain appropriately, it’s important first to address the type of pain the patient is experiencing so the clinician can choose the most appropriate therapy for the patient.
How Opioids Are Used Today for Pain
Opioids have been the subject of increased controversy over the last 20 years because of their contribution to our nation’s opioid and heroin crisis. Through µ-receptor agonism, opioids address pain at its many levels—opioids affect both the central and peripheral nervous system. However, exogenous opioids also mimic the body’s natural endorphins and, therefore, compete with their same receptor. It is this competitive agonism that effectively causes addiction in patients who chronically use opioids; patients attempt to use opioids to achieve a euphoria like that produced by endorphins. As patients continue to use opioids, they develop a tolerance, and higher doses are needed to achieve similar levels of euphoria and analgesia.
Opioid treatments for patients with chronic wounds can be administered orally, parenterally, or topically. Systemic opioids may be beneficial for patient populations that endorse multiple sources of pain. However, should the patient’s wound be the only source of pain, then topically applied opioids should be considered—especially since systemic opioid administration might result in intolerable side effects. Morphine can be topically applied in the form of a water-based gel, whereas methadone can be applied as an inert wound powder. The typical concentration for an opioid-based topical preparation is 1%.1,2 The amount of topical opioid used is dependent on many factors, including size of the wound, its severity, and the amount of exudate present.
While opioids can be an effective way to address pain for some patients, they are not without their unwanted side effects. Of note, chronic wound patients treated with opioids may experience decreased rates of healing.3 While the theory behind this delayed wound healing from opioid exposure is complemented with basic science research, additional translational and clinical research are warranted to determine if this relationship is causal.4–6 However, this is not to say that patients with chronic wounds should have their pain go untreated. In fact, undertreated pain may impact tissue perfusion and oxygenation and, therefore, delay wound healing.7,8 Pain remains an important outcome that must be thoroughly addressed in patients with chronic wounds. Therefore, it is imperative that wound clinicians take on a multi-faceted approach when it comes to acute and chronic pain management in patients with wounds.
Non-Opioid Pharmacologic Treatments
Multiple familiar non-opioid medications are efficacious individually and in combination for chronic pain. Significantly, acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce opioid requirements.9 Acetaminophen (Tylenol, Johnson and Johnson) inhibits central nervous system (CNS) prostaglandin synthesis and in 500 mg to 1 g thrice daily works to reduce mild to moderate pain.9 Of note, lower doses should be used as the analgesic response is not dose-dependent, and higher doses increase the risk of hepatoxicity.9 Acetaminophen, however, is the preferred method for advanced liver disease patients, but with a maximum dose not exceeding 2 g daily.9
NSAIDs work by inhibiting cyclooxygenase enzymes (COX-1 and COX-2) at the level of the spinal cord and peripheral terminal axons with the thought that COX-2 inhibition is responsible for anti-inflammatory and analgesic properties of NSAIDs and COX-1 inhibition linked to poor renal perfusion and gastrointestinal bleeding.9 Accordingly, NSAIDs should be avoided in patients with a glomerular filtration rate (GFR) <30, and those prone to GI bleeding. In patients >65 years with a history of peptic ulcer disease, a concomitant proton pump inhibitor (PPI) is recommended when using NSAIDs.9 Short-term use of low-dose celecoxib (Celebrex, Pfizer), a selective COX-2 inhibitor, has also demonstrated safety. However, it is advantageous to first try a different analgesic as selective COX-2 inhibitors have been shown to increase cardiovascular mortality.9
The combination of acetaminophen and NSAIDs, alternating between the two every 3 hours, has demonstrated excellent efficacy in managing pain in an adherent patient.9
Antidepressants, including serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs), may take weeks to show improvement in pain, but can be efficacious in managing neuropathic chronic pain.10 SNRIs for chronic pain venlafaxine (Effexor XR, Pfizer) (150–225 mg/day) and duloxetine (Cymbalta, Eli Lilly) (60–120 mg/day), are a safer option than TCAs by avoiding cardiac and anticholinergic adverse effects, especially in the elderly. TCAs, including amitriptyline (75–150 mg nightly) and the less-sedating nortriptyline (Pamelor, Mallinckrodt) and desipramine (Norpramin) (100–200 mg daily) have shown to be as effective as morphine and surpassing gabapentin’s efficacy.10,11 Girlon and colleagues also demonstrated that the combination of nortriptyline and gabapentin is superior in pain management than either alone.11
Gabapentin (Neurontin, Pfizer) and pregabalin (Lyrica, Pfizer) are anticonvulsants that work through the binding of presynaptic voltage gated calcium channels to treat neuropathic pain by decreasing the release of substance P, glutamate and calcitonin gene-related peptide (CGRP). Gabapentin (1,800-3,000 mg/day) and pregabalin (150-600 mg/day) can reduce pain 30–50% and by more when used in combination with medications previously described.9 When taken at night, gabapentin and pregabalin will also aid the patient in sleep.
Amplifiers of chronic pain, such as co-occurring disease, should be addressed when treating chronic pain. Therefore, the pharmacological treatment of pain should include treatments for comorbidities such as anxiety, depression, substance use disorder, obstructive sleep apnea, diabetes, among all others, to optimize overall health and pain control.
Targeted Interventional Therapies
Targeted interventional therapies such as nerve blocks, intra-articular steroid injections and surgery can be explored for the adjunctive treatment of chronic pain. A myofascial trigger point is a myofascial point that causes local and referred pain when manipulated.12 If necessary, trigger point injection can be performed with lidocaine, bupivacaine, onabotulinumtoxinA (Botox, Allergan) or dry acupuncture needles.12 Trigger points can also be manipulated via stretching or physical therapy.12 Trigger point therapy has shown promising results in treating headaches, temporal mandibular joint pain and myofascial pain syndrome.12
Another non-invasive interventional therapy, transcutaneous electrical nerve stimulation (TENS), works by applying electrical current to the skin at high and low frequencies to cause hypoalgesia. It is thought that TENS activates opioid receptors, inhibits central excitatory pathways and activates central inhibitory pathways.13,14 Although TENS is promising, a 2019 Cochrane Review demonstrated no clear evidence of either benefit or harm from the use of TENS for chronic pain.14 Further studies are needed to investigate the efficacy of both TENS and trigger point injections in the treatment of chronic pain and, specifically, in our wound patient population.
Complementary and Alternative Medicine (CAM) Therapies
Evidence-based complementary and alternative medicine (CAM) therapies remain an underutilized resource by physicians when treating chronic pain.
Non-pharmacologic treatments work to reduce pain through decreasing cortisol, epinephrine, and norepinephrine, as well as proinflammatory cytokines.9 Physical activation, whether through the patient’s preferred exercise routine, physical therapy, yoga, tai chi, or aqua therapy, is a safe and evidence-based treatment for chronic pain.15,16 Physical activity will not only improve pain, but will also improve overall mental and physical health.
Other evidence-based behavioral therapies for chronic pain management include healthy nutrition, adequate sleep hygiene, and cognitive exercises such as cognitive behavioral therapy (CBT), biofeedback, progressive muscle relaxation, mindfulness and meditation.17 As providers, we can familiarize ourselves with our local resources for CBT and mindfulness programs, as well as through phone and computer applications that can guide patients through these exercises.
One new and interesting analgesic technique exists in virtual reality (VR). For less than $40 on Amazon, physicians or patients can purchase a VR headset system for use during painful procedures such as debridement or dressing removal. During the procedure, the patient can experience a 3D visually and audibly immersive setting of their choosing. VR’s analgesic effect works through simple distraction, self-regulation and by inducing positive emotions.18,19 As VR has demonstrated promising results in acute pain, further studies are needed to show its impacts in chronic pain and long-term use.
Multiple interventional CAM modalities such as massage, chiropractic manipulation and acupuncture have been demonstrated success in treating chronic pain.20,21 Acupuncture, in particular, has been heavily studied.22 Auricular acupuncture, also known as battlefield acupuncture (BFA), has become increasingly utilized in chronic pain treatment. BFA has demonstrated clinical efficacy in treating chronic pain both immediately and 30 days after BFA treatment in a study of 112 subjects with chronic pain.23
Successful use of topical tetrahydrocannabinol (THC) and cannabidiol (CBD) to improve wound healing and its associated pain have been reported. Cannabinoid receptors are found throughout the skin and its immune cells.24 Because CBD and wounds lacking epithelium are both non-polar and lipophilic, CBD is easily absorbed through wounds.25 Further randomized controlled trials are needed to show both CBD and THC efficacy in wound healing and the treatment of chronic wound pain.
Despite the demonstrated clinical efficacy of many CAM therapies in the treatment of chronic pain, not all insurance plans cover CAM. More studies are warranted to demonstrate the clinical efficacy of these therapies in chronic wound patients to gain insurance and further physician acceptance.
Clinical Pearls for Wound Pain Management
• Identify the patient’s source of pain: nociceptive, neuropathic, or infectious
• Create a multi-modal approach with both medication and adjunctive CAM therapies
• Optimize non-opioid pharmacologic and non-pharmacologic adjunctive treatments before considering opioids
• Have an informed discussion of the risks of opioid use with the patient before prescribing
• Encourage a nutritious diet and physical activity to the patient’s ability
An important part of treating our patient population is not only healing their wounds but also treating their associated pain. Wound care visits provide consistent and ample time, especially when applying dressings, when an integrative, multimodal approach to pain can be discussed. Further studies are needed to show the definitive clinical efficacy of these techniques in treating wound specific pain. However, many of these methods have shown promising results in chronic pain patients and may be worth pursuing in our wound patient population.
Caralin Schneider, BA, is a Wound Clinical Research Fellow at the University of Miami Miller School of Medicine.
Scott Stratman, BS, is a Wound Clinic Research Fellow at the University of Miami Miller School of Medicine.
Hadar A. Lev-Tov, MD, MAS, is an Assistant Professor in the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery at University of Miami Miller School of Medicine.
Daniel Federman, MD, is a Professor of Medicine at Yale School of Medicine and Chief of Medicine at VA Connecticut Healthcare System.
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