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Inflammation and Pain

Practice Accelerator
July 22, 2021

Wounds typically heal in four sequential but overlapping phases — hemostasis, inflammatory, proliferative and remodeling — ultimately leading to tissue regeneration.1 Healing sometimes stalls for various reasons, a key one being extensive inflammation, which disrupts the normal cascade of healing and leads to chronic and hard-to-heal wounds. A vicious cycle of ongoing inflammation, pain and poor quality of life often follows. Understanding how to break this cycle is essential for wound care clinicians who want to optimize healing outcomes and patient quality of life.

Chronic Inflammation

Chronic and hard-to-heal wounds can be treated with appropriate and combined modalities early on. A comprehensive assessment is necessary and should address the underlying etiologies for chronic and hard-to-heal wounds, which may include venous leg ulcer, arterial ulcer, pressure injury or diabetic foot ulcer, all of which can be exacerbated by aging, bacterial colonization, hypoxia and ischemia reperfusion injury. The resulting increases in neutrophils, macrophages, protease inhibitors, inflammatory cytokines and reactive oxygen species (ROS), along with decreased growth factor availability and extracellular matrix destruction, create yet another vicious cycle of inflammation and wounds that fail to heal.1 Neutrophil infiltration, a central culprit in chronic inflammation and a biological marker of chronic wounds, is a major cause of tissue damage.2,3 Other contributors include local tissue hypoxia, bioburden/biofilm and repetitive trauma. Eliminating the factors that underlie inflammation can promote healing in chronic wounds.5

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In addition, using a systematic, structured approach to wound management will help prevent and overcome barriers to healing. Elements of such an approach include adequate wound bed preparation and proper nutrition.1 The goals of wound management are to resolve chronic inflammation by removing its cause(s), to promote healthy granulation tissue formation and to transform the chronic state into an acute state, all of which will move the wound toward healing.

Pain and Pain Management

Patients with chronic or hard-to-heal wounds may experience acute or chronic pain. The prevalence of pain in patients with chronic wounds is 54% to 87%, with up to 67% of patients reporting severe pain.6 The pain may be intermittent or continuous, and it can be exacerbated by wound manipulation during dressing changes or debridement.7 Identifying the cause of pain is key to properly managing it. A thorough pain assessment is indicated to determine whether the pain stems from an underlying disease process (e.g., diabetic peripheral neuropathy), the wound itself, poor circulation and/or chronic inflammation.8 Chronic pain can lead to depression, anxiety and isolation, which can further lengthen wound duration by increasing stress and compromising the patient’s immune response.6,9 Managing patients’ pain can be difficult. Although oral opioid use remains controversial, other formulations can be applied topically to the wound, such as a morphine or methadone powder or gel.14,11

Topical tetrahydrocannabinol (THC) and cannabidiol (CBD) reportedly have been used successfully to heal wound-associated pain, but further randomized, controlled trials are needed.12 Over-the-counter pain relievers (e.g., acetaminophen, ibuprofen) are commonly prescribed to help patients manage their wound pain or dressing changes, and they are considered safe for patients if they take the prescribed dosages. Patients should avoid aspirin products to minimize bleeding. Topical lidocaine gels or injections can help reduce the sensation of pain in wound tissue. They are low cost and cause minimal side effects during short-term use; however, further studies are warranted to determine the impact of long-term use.13 Practicing “pain-free” dressing change strategies can also help patients manage their pain. Various types of dressings can help reduce pain, including hydrogels, calcium alginates, hydrocolloids, foams and transparent film. The advantages to some of these dressings are longer wear times (hydrocolloids, foams, transparent films, alginates) and soothing effects (hydrogels). Other strategies and products to support pain-free dressing changes include the following:

  • Changing dressings in a timely manner
  • Applying periwound protectants
  • Using warm normal saline/non-cytotoxic cleansers
  • Offloading
  • Avoiding tapes
  • Using anti-shear dressings
  • Administering pain medications around the clock or 30 minutes prior to dressing change
  • Using distraction techniques and time-outs
  • Using moist wound therapy
  • Talking to the patient about the dressing change process15


Stalled wound healing and the accompanying pain can have more than a physical impact on patients and may lead to depression, anxiety and feelings of isolation. Treating the whole patient using an integrative, multimodal approach will help optimize overall healing outcomes and clinical efficacy. Clinicians can mitigate the impact of wounds on patients by creating a plan for pain management and an aggressive treatment approach to achieve wound closure more quickly.

August is Biofilm and Inflammation Month


1. Zhao R, Liang H, Clarke E, Jackson C, Xue M. Inflammation in Chronic Wounds. Int J Mol Sci. 2016;17(12):2085.

2. Diegelmann RF, Evans MC. Wound healing: An overview of acute, fibrotic and delayed healing. Front. Biosci. 2004;9:283-289.

3. Renner R, Erfurt-Berge C. Depression and quality of life in patients with chronic wounds: ways to measure their influence and their effect on daily life. Chronic Wound Care Management and Research. 2017;4:143-151.

4. Stojadinovic A, Carlson JW, Schultz GS, Davis TA, Elster EA. Topical advances in wound care. Gynecol Oncol. 2008 Nov;111(2 Suppl):S70-S80.

5. Goldman R. Growth factors and chronic wound healing: Past, present, and future. Adv. Skin Wound Care. 2004;17:24-35.

6. Phillips T, Stanton B, Provan A, et al. A study of the impact of leg ulcers on quality of life: financial, social, and psychologic implications. J Am Acad Dermatol. 1994;31(1):49-53.

7. Woo K, Sibbald G, Fogh K, et al. Assessment and management of persistent (chronic) and total wound pain. Intl Wound J. 2008;5(2):205-215.

8. Hoffman D, Ryan T, Arnold F, et al. Pain in venous leg ulcers. J Wound Care. 1997;6(5):222-224.

9. Woo, KY. Exploring the effects of pain and stress on wound healing. Adv Skin Wound Care. 2012;25(1): 38-44, quiz 45.

10. Twillman RK, Long TD, Cathers TA, Mueller DW. Treatment of painful skin ulcers with topical opioids. J Pain Symptom Manage. 1999 Apr;17(4):288-292.

11. Gallagher RE, Arndt DR, Hunt KL. Analgesic effects of topical methadone: a report of four cases. Clin J Pain. 2005 Mar-Apr;21(2):190-192.

12. Toth KF, Adam D, Biro T, Olah A. Cannabinoid signaling in the skin: therapeutic potential of the “c(ut)annabinoid” system. Molecules. 2019;24(5):918.

13. Treadwell T, Walker D, Nicholson BJ, Taylor M, Alur H. Treatment of Pain in Wounds with a Topical Long Acting Lidocaine Gel. Chronic Wound Care Management and Research. 2019;6:117-121.

14. How to Make Dressing Changes Less Painful, Adv Skin Wound Care. 2004;17(1):42-43. 

The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, HMP Global, its affiliates, or subsidiary companies.