Meeting the Challenges of Wound-associated Pain: Anticipatory Pain, Anxiety, Stress, and Wound Healing

   Pain is an unpleasant physical and emotional experience that plays a key role in the lives of people with chronic wounds.^1-3 It is well documented that the majority of patients with chronic wounds suffer from moderate to severe pain for a protracted period of time with frequent exacerbations.^4-8 Although pain often is associated with conditions intrinsic to underlying etiologies (eg, acute lipodermatosclerosis in venous leg ulcers, Charcot changes with diabetic foot ulcers), trauma (pressure, shear, and friction), chemical irritation, infection, or inflammation, spontaneous pain may occur due to sensitization of nerve fibers.⁹ In studies conducted during dressing changes, patients describe the most excruciating pain at dressing removal as aggressive adhesives are peeled away from fragile and damaged periwound skin.^10-13 Increasing evidence also validates pain with wound cleansing, especially when abrasive materials or forceps are used to remove debris from the wound bed.^3,14,15    To raise awareness and promote a systemic approach to managing pain, Woo and Sibbald² developed a wound-associated pain (WAP) model that highlights three key components: the wound, the cause, and the patient (see Figure 1). First, the underlying cause of the wound-associated pain must be treated.^2,16 Second, local wound care issues that may exacerbate wound-associated pain must be addressed. These include tissue trauma (dressing removal and wound cleansing)^5,17,18; moisture balance (too much moisture can cause skin maceration and erosion while too little moisture dries out the dressing that then tends to adhere to wound bed)³; infection/inflammation (increased pain is a warning sign for potential deep wound infection)^19,20; and patient-centered concerns (eg, anxiety, depression, anticipation of pain).^21-24

   While a plethora of advanced wound care products and treatment modalities has been developed over the years, little attention is paid to patient factors that can modulate pain and wound healing. Experimental and clinical studies of pain^25-28 elucidate that the same stimulus does not always evoke the same experience of pain. Variability in pain perceptions can be influenced by many contextual and psychological (patient-centered) factors. Accumulating evidence has demonstrated that anxiety in relation to anticipation of impending pain can lead to increased self-reported pain intensity, reduced pain tolerance, and decreased pressure pain thresholds.^29,30 With heightened anxiety, environmental and somatic signals are brought to the patient’s attention, sharpening the degree of sensory receptivity. Similar to the concept of a self-fulfilling prophecy, the term nocebo effect (versus placebo effect) is used to connote the phenomenon in which pain is incurred or intensified by patients’ anticipation or expectation.^31-33

The Pathophysiology of Anticipated Pain

   Anticipation of pain and associated anxiety are more than psychological phenomena. They have been demonstrated to trigger the activation of cholecystokinin, which plays a crucial role in pain transmission.³³ Neuroimaging studies documented that the anterior cingulate cortex, the prefrontal cortex, and the insula are activated during the anticipation of pain, suggesting a specific neurocircuitory connection. Anxiety also may reduce the descending inhibition signals, allowing pain to gain access through the “gate control mechanism” to the central nervous system.³⁴

   How do anxiety and anticipation of pain affect wound healing? Psychological stress as result of pain and anxiety activates the hypothalamic-pituitary-adrenal (HPA) axis and cortisol production. The hormone glucocorticoid modulates immune cells by suppressing differentiation and proliferation, down-regulating gene transcription and reducing expression of cell adhesion molecules that are essential for cell trafficking.^35,36

   Deficient inflammatory response will hamper the body’s defense against invading organisms and removal of debris from wound bed for tissue regeneration. Several studies have demonstrated the association between stress and impaired healing. Kiecolt-Glaser³⁷ compared wound healing in 13 women caregivers who had a relative with Alzheimer’s Disease to 13 controls matched for age. Time to achieve complete closure of biopsy-induced wounds was 9 days longer in the caregiver versus control groups due to caregiving stress (P < 0.05). Marucha et al³⁸ documented that the average complete wound healing time was significantly longer in 11 students during stressful examinations (P < 0.001). Garg et al³⁹ observed that skin barrier recovery rate from damage caused by tape stripping was significantly slower during a high versus low stress period (P < 0.001). Glaser and his team⁴⁰ examined psychological stress and the levels of proinflammatory cytokines in experimentally-induced skin blisters on the forearms of 36 women. Women who reported high stress produced significantly lower levels of IL-1alpha (P < 0.03) and Il-8 (P < 0.04). On the other hand, chronic and repeated stress/pain may attenuate the HPA axis feedback mechanism. The result is excess inflammatory response and end-products (eg, MMPs) that stall wound healing.

   In a cross-sectional study of patients with leg ulcers (n = 190), Jones et al⁴¹ examined the relationships between anxiety, living alone, mobility, exudate, and pain. Only pain and anxiety were significantly related. Woo et al¹⁰ examined pain, anxiety, and anticipatory pain in 96 patients with chronic wounds. The subjects were asked to rate their levels of anticipatory pain and actual pain levels at different times during wound care using a numerical rating scale. Anxiety was measured by Spielberger’s State Anxiety Inventory.⁴² During dressing change, patients rated cleansing and dressing removal as the most painful. Consistent with previous findings, the higher the anxiety before dressing change, the higher the anticipatory level of pain and the more intense the pain expressed during the procedure (P = 0.000), a significant correlation. Linear regression identified anxiety as a significant predictor of mean pain scores, accounting for 25.7% of variance.

Implication for Practice

   Anxiety-reduction techniques include relaxation, music, touch therapy, visual stimulation, hypnosis, stress-reducing strategies, guided imagery, behavioral and cognitive therapy, and distraction. These techniques have been suggested as options for managing wound pain.⁴³ In addressing anxiety and anticipation of pain, the importance of the therapeutic relationship between patients and healthcare providers cannot be underestimated. Clinicians must recognize that certain individuals are more likely to overestimate pain, making them susceptible to anxiety. Before initiating any wound care procedures, adequate information tailored to individual level of understanding should be provided. To mitigate pain, it is important to:
     • Engage patients, their families, and other caregivers by talking about their pain and concerns about debridement
     • Empathize about the impact of pain
     • Educate patients by explaining why the procedure is required and how it is done
     • Enlist their participation by allowing the patient to actively participate during the procedure and call time outs. (Table 1).⁴⁴

1. Woo K, Sibbald RG. Managing wound-associated pain with “DIME” and a patient-focused toolkit. D.I.M.E. Pain and wound bed preparation: from patient-centered concerns to D.I.M.E. Compliments of Molnlycke Healthcare, Gothenburg, Sweden. 2007:1-4.

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

3. Woo KY, Harding K, Price P, Sibbald G. Minimising wound-related pain at dressing change: evidence-informed practice. Int Wound J. 2008;5(2):144–157.

4. Price PE, Fagervik-Morton H, Mudge EJ, et al. Dressing-related pain in patients with chronic wounds: an international patient perspective. Int Wound J. 2008;5(2):159–171.

5. Meaume S, Téot L, Lazareth I, Martini J, Bohbot S. The importance of pain reduction through dressing selection in routine wound management: the MAPP study. J Wound Care. 2004;13(10):409–413.

6. Husband LL. Shaping the trajectory of patients with venous ulceration in primary care. Health Expect. 2001;4:189–198.

7. Nemeth KA, Harrison MB, Graham ID, et al. Understanding venous leg ulcer pain: results of a longitudinal study. Ostomy Wound Manage. 2004;50(1):34–36.

8. Günes UY. A descriptive study of pressure ulcer pain. Ostomy Wound Manage. 2008; 54(2):56–61.

9. Woo KY, Sibbald RG. Chronic wound pain: a conceptual model. Adv Skin Wound Care. 2008;21(4):175–188.

10. Woo K, Sadavoy J, Sidani S, Maunder R, Sibbald RG. The relationship between anxiety, anticipatory pain, and pain during dressing change in the older population. Presented at the CAWC Annual Conference. London, Ontario. November 1-4, 2007.

11. Szor JK, Bourguignon C. Description of pressure ulcer pain at rest and at dressing change. J Wound Ostomy Continence Nurs. 1999;26(3):115–120.

12. Price P, Fogh K, Glynn C, Krasner DL, Osterbrink J, Sibbald RG. Managing painful chronic wounds: the Wound Pain Management Model. Int Wound J. 2007;4(suppl 1):4–15.

13. Dykes PJ, Heggie R. The link between the peel force of adhesive dressings and subjective discomfort in volunteer subjects. J Wound Care. 2003;12:260–262.

14. Briggs M. Examining equipment for wound care: the use of forceps and cotton wool in dressing packs. Accid Emerg Nurs. 1994;2:237–239.

15. Ernst A, Gershoff L, Miller P. Warmed versus room temperature for laceration irrigation: a randomized clinical trial. South Med J. 2003;96:436–439.

16. Freedman G, Entero H, Brem H. Practical treatment of pain in patients with chronic wounds: pathogenesis-guided management. Am J Surg. 2004;188:31–35.

17. Hollinworth H, Collier M. Nurses’ views about pain and trauma at dressing changes: results of a national survey. J Wound Care. 2000;9:369–373.

18. Dykes PJ, Heggie R, Hill SA. Effects of adhesive dressings on the stratum corneum of the skin. J Wound Care. 2001;10(2):7–10.

19. Gardner SE, Frantz RA, Troia C, et al. A tool to assess the clinical signs and symptoms of localized infection in chronic wounds: development and reliability. Ostomy Wound Manage. 2003;49(4 suppl):24–29.

20. Landis S, Ryan S, Woo K, Sibbald RG. Infections in chronic wounds. In: Krasner DL, Rodeheaver GT, Sibbald RG. Chronic Wound Care: A Clinical Source Book for Healthcare Professionals, 4th edition. Malvern, Pa: HMP Communications;2007:299–323.

21. Weinberg K, Birdsall C, Vail D, et al. Pain and anxiety with burn dressing changes: patient self-report. J Burn Care Rehabil. 2000;21:155–156.

22. Jones J, Barr W, Robinson J, et al. Depression in patients with chronic venous ulceration. Br J Nurs. 2006;15:S17–23.

23. Benedetti F. Mechanisms of placebo and placebo-related effects across diseases and treatments. Annu Rev Pharmacol Toxicol. 2008;48:33–60.

24. Roth RS, Lowery JC, Hamill JB. Assessing persistent pain and its relation to affective distress, depressive symptoms and pain catastrophizing in patients with chronic wounds: a pilot study. Am J Phys Med Rehabil. 2004;83:827–834.

25. Kenntner-Mabiala R, Andreatta M, Wieser MJ, Mühlberger A, Pauli P. Distinct effects of attention and affect on pain perception and somatosensory evoked potentials. Biol Psychol. 2008;78(1):114–122.

26. Loggia ML, Mogil JS, Bushnell MC. Empathy hurts: compassion for another increases both sensory and affective components of pain perception. Pain. 2008;136(1-2):168–176.

27. Kut E, Schaffner N, Wittwer A, et al. Changes in self-perceived role identity modulate pain perception. Pain. 2007;131(1-2):191–201.

28. Miller C, Newton SE. Pain perception and expression: the influence of gender, personal self-efficacy, and lifespan socialization. Pain Manag Nurs. 2006;7(4):148–152.

29. Feeney SL.The relationship between pain and negative affect in older adults: anxiety as a predictor of pain. J Anxiety Disord. 2004;18(6):733–744.

30. Gore M, Sadosky A, Leslie D, Sheehan AH. Selecting an appropriate medication for treating neuropathic pain in patients with diabetes: a study using the UK and Germany mediplus databases. Pain Pract. 2008;8(4):253–262.

31. Enck P, Benedetti F, Schedlowski M. New insights into the placebo and nocebo responses. Neuron. 2008;31;59(2):195–206.

32. Petrovic P. Placebo analgesia and nocebo hyperalgesia—two sides of the same coin? Pain. 2008;136(1-2):5–6. Comment on: 211–218.

33. Colloca L, Benedetti F. Nocebo hyperalgesia: how anxiety is turned into pain. Curr Opin Anaesthesiol. 2007; 20(5):435–439.

34. Melzack R. Recent concepts of pain. J Med. 1982;13(3):147–160.

35. Blackburn-Munro G. Hypothalamo-pituitary-adrenal axis dysfunction as a contributory factor to chronic pain and depression. Curr Pain Headache Rep. 2004;8(2):116–124.

36. Sternberg EM. Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nat Rev Immunol. 2006;6(4):318–328.

37. Kiecolt-Glaser JK, Marucha PT, Malarkey WB, Mercado AM, Glaser R. Slowing of wound healing by psychological stress. Lancet. 1995;346(8984):1194–1196. Comment in: Lancet. 1996;347(8993):56.

38. Marucha PT, Kiecolt-Glaser JK, Favagehi M. Mucosal wound healing is impaired by examination stress. Psychosom Med. 1998;60(3):362–365.

39. Garg A, Chren MM, Sands LP, et al. Psychological stress perturbs epidermal permeability barrier homeostasis: implications for the pathogenesis of stress-associated skin disorders. Arch Dermatol. 2001;137(1):53–59. Comment in: Arch Dermatol. 2001;137(1):78–82.

40. Glaser R, Kiecolt-Glaser JK, Marucha PT, MacCallum RC, Laskowski BF, Malarkey WB. Stress-related changes in proinflammatory cytokine production in wounds. Arch Gen Psychiatry. 1999;56(5):450–456.

41. Jones J, Barr W, Robinson J, Carlisle C. Depression in patients with chronic venous ulceration. Br J Nurs. 2006;15(11):S17–S23.

42. Spielberger CD. Preliminary Manual for the State-Trait Personality Inventory (STPI). University of South Florida;1979.

43. Krasner D.The chronic wound pain experience: a conceptual model. Ostomy Wound Manage. 1995; 41(3):20–25.

44. Keller VF, Carroll JG. A new model for physician-patient communication. Patient Educ Couns. 1994;23:131–140.