At present, there are few local options for the treatment of persistent pain, while managing the exudate levels present in many chronic wounds. Important properties of such local options are that they provide an optimal wound healing environment, while providing a constant local low-dose release of ibuprofen during weaning time. Various local topical drug-releasing regimes have shown to be effective in reducing the pain of chronic leg ulcerations. Use of ibuprofen slow-release foam dressings for persistent venous leg ulcer has shown improvement in terms of pain relief and quality of life. Ibuprofen gel when applied to chronic venous leg ulceration resulted in overall reduction of pain and improved mobility, sleep, and mood during the treatment, but the pain intensity increased in 1 week after discontinuing treatment. The release of ibuprofen is limited in a dry wound environment, and therefore the presence of dry necrotic tissue will impede any pain reduction [19]. Likewise, topical use of eutectic mixture of local anesthetics prilocaine-lignocaine (EMLA 5 %) has also shown improvement in pain scores and quality of life. Oral medications may be supplemented with topical aesthetic preparations [20] although they should be used with caution in open wounds because of increased absorption. Topical preparations used are eutectic mixture of local anesthetics applied 30–60 min before debridement under occlusion with a film dressing (not approved by the Food and Drug Administration for use in open wounds in the United States), 4 % lidocaine solution, 2 % lidocaine gel, 1 % lidocaine solution, 5 % lidocaine patch, topical diclofenac patch, and morphine topical gel [20].

The first line of pain treatment in patients with chronic wounds should be non-pharmacological. Changes in positioning, gentle wound cleansing, use of different types of dressing, and distraction or relaxation techniques have been shown to ease discomfort of cyclic pain during procedures. No pharmacological methods reduce anxiety and stress, thereby allowing the body to naturally readjust pain perception and raise tolerance to future treatment.

Transcutaneous electrical nerve stimulation (TENS) has been used as a noninvasive, non-pharmacologic adjuvant treatment modality for chronic ischemic pain [21–23]. Electrodes stimulate non-nociceptive fibers to decrease pain. A lasting reduction of pain with the use of low-frequency ultrasound has been shown in patients with recalcitrant venous leg ulcers [24]. Noncontact ultrasound has long been reported to decrease the mean healing time of chronic lower extremity wounds. Significant reduction in pain has been noted after using noncontact ultrasound for control of painful wounds [25–28]. Pulsed radiofrequency energy has been used as an adjuvant treatment in the healing of diabetic foot and pressure ulcers [29–32]. The mechanism by which pulsed radiofrequency energy alleviates pain is largely unknown. It has been demonstrated to increase the expression of cytokines (interleukin-related genes) and tumor necrosis factor-related genes that help to potentiate an initial inflammatory response production of anti-inflammatory cytokines (interleukin 10) as well as hemeoxygenase 1,2 (an off-switch for inflammation) which results in the release of potent antioxidants, antiapoptotic, and anti-inflammatory agents [33]. Pulsed radiofrequency energy (PRFE) treatment is done usually at home with an applicator pad placed directly over the wound dressing. The applicator pad delivers regulated, nonthermal radiofrequency energy at 27.12 MHz consisting of 42 μs pulses delivered 1000 times per second. Treatments last 30 min and are performed twice.

Chronic background pain should be controlled quickly using oral analgesics. Patients exhibit a general reluctance to take oral analgesia due to concerns about side effects and dependency and confusion about administration and dosages. The World Health Organization (WHO) provided guidelines for the treatment of cancer pain in titrating the type and dose of analgesia to the level of pain. These guidelines can be applied to wound pain. The recommended steps for control of wound pain include:

Ideally, analgesics should be fast acting, easily titrated to require changes, and have minimal side effects. Persistent chronic pain associated with nonhealing wounds is caused by tissue (nociceptive) or nerve (neuropathic) damage and is influenced by dressing changes and chronic inflammation. Anticonvulsants and sodium channel blockers have been shown to be effective in neuropathic as well as nociceptive pain. The use of gabapentin, a voltage-sensitive sodium and calcium channel blocker, also has been used as a co-analgesic to morphine in a patient with cancer wound dressing pain [33]. Oral medications may be supplemented with topical anesthetic preparations, although they should be used with caution in open wounds because of increased absorption.

Mashiah et al. performed phenol lumbar sympathectomy on 373 patients with painful leg ulcers, of whom 226 (60.6 %) were diabetic [36]. Over 24–120 months of follow-up, 219 patients (58.7 %) experienced total relief from pain and healing of gangrenous ulcers, although the treatment was unsuccessful in 154 patients. A favorable result was marked in diabetic patients who had rest pain and in nondiabetic patients who had digital gangrene or digital ulcers. Age and sex did not affect the results, but heavy smoking did affect. Phenol sympathectomy should be considered as an alternative to surgical sympathectomy [37]. Furthermore, the technique may be a precursor to and even an alternative to amputation in patients who have diabetes and advanced arteriosclerosis of the lower limb. Cross et al. noted pain relief in rest pain in two third (66.67 %) of patients of critical limb ischemia undergoing chemical sympathectomy in treatment group as compared to 23.5 % in control group at 6 months interval [38]. Although reduction in vascular peripheral resistance was shown, no difference in ankle–brachial pressure index or graft survival was demonstrated [39]. Fify and Quin (1975) in a randomized trial using phenol sympathectomy versus local anesthetic controls in patients with intermittent claudication found no subjective or objective difference between two groups at 1–3 months interval [40]. Alexander showed encouraging result (72 %) improvements in patients with peripheral vascular disease undergoing chemical sympathectomy with an amputation rate of 24 % [41].

Lumbar sympathectomy has been employed for over 75 years for the treatment of a variety of painful and circulatory conditions in the lower extremities. Chemical sympathectomy decreased the need for open surgical sympathectomy with less morbidity and mortality but still has risks and complications that can be catastrophic. The development of precise neurolysis with radiofrequency significantly decreased the risks of sympathectomy with results comparable to chemical and surgical neuroablation [42]. Radiofrequency sympathectomy also allows repeat procedures without the risk of distorting the original anatomy.

It has been frequently observed that the results of surgical sympathectomy are better than indicated by the diagnostic block. Also the beneficial effect of sympathectomy is progressive over a period of several weeks. Since a diagnostic block with most agents lasts only for 2–3 h, this may not be of sufficient time to permit more than a token improvement in collateral circulation. A phenol sympathetic block, which persists for several weeks, seems to be a more rational approach to evaluating patient to be good candidate for surgery. In addition to pain reduction, lumbar sympathectomy has been used as a vasodilator to increase blood supply to the legs in patients with ischemic peripheral arterial disease. It has been noted to improve tissue oxygenation and ulcer healing and decrease pain by interrupting sympathetic–nociceptive pairing. Decrease in pain between 35 and 85 % has been noted 6 months after lumbar sympathectomy [43]. A recent study found that most physicians in the United Kingdom believe that lumbar sympathectomy is an effective, inexpensive, and safe procedure for the treatment of lower extremity ischemia [44]. Chemical lumbar sympathectomy has been shown to be an effective alternative to surgical sympathectomy [36].