“Phantom Skin Pain” Neuropathic Pain Following Burn Injury – An Examination of Incidence and Treatment

Background Severe burn injury impacts heavily on an individual’s physical, psychological and social integrity. The pain following this injury can be severe, distressing and difficult to manage with a combination of inflammatory pain, procedural pain and pain due to nerve injury and dysfunction. The focus of this research is the concept, incidence, aetiology, treatment and prevention of neuropathic pain after burn injury. Aims This research had several aims: 1. Review the medical literature on pain after burn injury with a emphasis on the neuropathic component 2. Determine the nature and quality of acute pain after burn injury 3. Collect data and publish a case series on the use of gabapentin in burn-injured patients 4. Conduct a randomised controlled trial of pregabalin to determine safety and efficacy in the management of burn-injury pain 5. Determine if pregabalin, given at the time of a clinical burn injury, will decrease the incidence of persistent pain 6. Propose an animal model that will further investigate the underlying mechanism of pain after burn injury 7. Raise awareness of this clinical challenge through promoting the phrase “Phantom Skin Pain” as a reasonable clinical term to use for patients and healthcare workers 8. Propose a burn pain assessment tool Methods Following is the methodology for each aim: 1. Search of medical literature using Ovid Medline and Google Scholar with keywords: ‘burn injury’, ‘thermal injury’, ‘pain’, ‘pain management’, ‘gabapentin’, ‘pregabalin’ and ‘phantom skin pain’ 2. The Neuropathic Pain Scale (NPS) was utilised in a survey of patients after burn injury to determine the intensity, nature and quality their pain experience 3. Medical records of six patients given gabapentin following burn injury were reviewed, assessing their pain experience and response to gabapentin 4. A randomised double-blind placebo-controlled trial to assess the efficacy and tolerability of pregabalin to alleviate the neuropathic component of moderate to severe burns pain was conducted. Patients aged 18 to 65 years admitted to the Burns Unit with a 5% or greater total body surface area burn injury were screened to participate in the trial. The NPS was again utilised; if patients scored 4 or higher on the primary outcome measures of ‘sharp’ or ‘hot’ pain, they were invited to participate in the trial. Consenting patients were randomly assigned to receive pregabalin or placebo for 28 days with individual dose titration commencing at 75mg bd to a maximum of 300mg bd. Secondary outcome measures included the remaining elements of the NPS, daily opioid requirement, length of hospital stay and side-effects of nausea, vomiting, drowsiness and giddiness. 5. Patients in the pregabalin RCT were followed up at 6 months to determine incidence of long-term pain. 6. The literature was reviewed for a possible burn-injury animal model that further defined the mechanism of action of gabapentin and pregabalin. 7. The previous use of the term ‘phantom skin pain’ was investigated in the medical and lay literature. 8. Review the common and important symptoms of burn injury pain in the context of existing pain scales. Results and Conclusions Presented below are the results for each aim: 1. Animal and human burn injury models suggest that secondary hyperalgesia from central sensitisation is an important part of burn pain pathophysiology. In addition, several mediators may play an important role, including TRPV1, IL-6 and microglial activation. 2. The NPS demonstrated that patients after burn injury scored highly for ‘skin sensitivity’, ‘unpleasantness of the pain’, ‘surface pain’, ‘intensity of the pain’, ‘sharp pain’ and ‘hot pain’. 3. Six burn-injured patients responded well to gabapentin in reducing neuropathic pain. The data from this small case series with a discussion has been published. 4. The randomised placebo-controlled trial demonstrated that pregabalin significantly reduced the primary outcome measures of ‘hot’ and ‘sharp’ pain. Secondary outcome measures that improved when compared to the placebo were ‘itch’, ‘unpleasantness’ and ‘surface’ pain. Adverse effects were uncommon with no difference between the treatment groups. There was no significant difference between the groups for opioid consumption or duration of hospital stay. 5. Patients in the pregabalin trial were followed up at 6-months. There was no statistically significant difference in the incidence of pain between the pregabalin (24%) and placebo (29%) groups. 6. Following review of the literature, an animal model was proposed that involved a scald burn to a unilateral hind-paw followed by western blot and immunohistochemical analysis of the expression of the α2-δ type 1 subunit of the neuronal voltage-gated calcium channel. This unit upregulates in neuropathic pain models but has not been examined in a burn injury model. This may explain, in part, the antihyperalgesic mechanism seen with gabapentin and pregabalin. 7. The phrase ‘phantom skin pain’ was first coined in 1991; since that time, it has not been utilised consistently. It is proposed that the phrase be adopted to describe acute and persistent burn-injury pain of a neuropathic nature. 8. A Burn Pain Assessment Tool was developed and awaits validation