The peripheral nervous system is composed of 43 pairs of nerves: 12 pairs of cranial nerves and 31 pairs that enter the spinal cord and become spinal nerves. Peripheral nerves have afferent and efferent fibers. The afferent fibers carry impulses from the periphery to the central nervous system for processing. After the brain interprets the sensory input carried from the afferent nerve fibers, an impulse is sent via the efferent nerve fibers.

Peripheral neuropathy is inflammation, injury, or degeneration of the peripheral nerve fibers, and it occurs commonly in patients with cancer. One study found that 48% of patients with lung cancer had peripheral neuropathy before beginning chemotherapy. A number of chemotherapeutic agents are known to cause peripheral neuropathy: 50% of individuals receiving vincristine develop paresthesias of the hands and feet, and 20%–90% of patients receiving cisplatin develop neuropathy. The development of cisplatin-induced neuropathy is dependent on the dose of the drug received. Sixty-two percent of patients receiving paclitaxel develop neuropathies.

Peripheral neuropathy is characterized by several symptoms. Paresthesias are abnormal, intermittent, but nonpainful sensations, perceived spontaneously or evoked by a stimulus. Dysesthesias are characterized as abnormal, noxious sensations. Another unique finding is allodynia, which may be mechanical or thermal. Allodynia is the painful response to an ordinarily non-noxious stimulus, such as clothing, the mere movement of air, touch, or the nonpainful application of cold or warm stimulus. Mechanical allodynia is pain caused by mechanical stimuli to the skin that normally are not painful. Hyperalgesia is a symptom of neuropathy and is an exaggerated response to a painful stimulus. Sensory examination is extremely important. Not only should practitioners understand and confirm the location of neuropathic pain and its distribution, but they also should understand the major nerves that are involved if possible.

In addition to normal touch, pain, temperature, and vibration sensory testing, practitioners should pay attention to light touch to assess for the presence or absence of allodynia. In a patient with a distal symmetric sensorimotor neuropathy, sensory examination shows reduced sensitivity to light touch, pinprick, and temperature in a stocking-glove distribution. Vibration and position sense are reduced in the distal legs prior to involvement of the arms.

The motor system also is crucial in neurologic assessment. The presence of atrophy in assessing muscle bulk is important because it tells practitioners a little about the types of nerves that have been injured or inactive. The lack of atrophy does not mean, however, that neural injury has not occurred. Muscle strength, coordination, and gait all must be taken into account. Deep tendon reflexes should be examined for the presence or absence of reflexes. Hyporeflexia can occur to affected peripheral nerves.

The role of the autonomic nervous system must be taken into account when examining patients. Practitioners might notice a difference in limb temperature (one extremity being hotter or cooler than the others), abnormal sweating, hair or nail growth abnormalities, and skin color changes. All are signs of autonomic dysfunction or problems with regulation and go along with neuropathic problems.

Practitioners also assess for a rebound effect of the pulse rate after performing the Valsalva maneuver; the absence of a rebound quickening of the pulse may suggest that autonomic dysfunction exists. Intestinal motility is assessed by asking about recent bowel habits versus normal bowel patterns. With autonomic dysfunction, peristalsis may slow down and lead to constipation. Upon auscultation, nurses may notice hypoactive bowel sounds. Vinca alkaloids such as vincristine can cause the problem.

Blood pressure should be taken while patients lie, sit, and stand to check for orthostatic changes. A decrease in the systolic blood pressure of > 20mm Hg is indicative of orthostatic hypotension.

Sexual dysfunction can be assessed by asking men about their ability or inability to have spontaneous erections. If a man is able to have a spontaneous erection but not able to have an erection during intimate sexual activity, he may be incapable of the latter because of psychological issues rather than neuropathic issues. If he is unable to have a spontaneous erection, the dysfunction may be caused by autonomic neuropathy.

Oxman, M., Levin, M.J., Johnson, G.R., Schmader, K.E., Straus, S.E., Gelb, L.D., et al. (2005). A vaccine to prevent herpes zoster and postherpetic neuralgia. New England Journal of Medicine, 352, 2271–2282.

Bibliography

Argoff, C., Katz, N., & Backonja, M. (2004). Treatment of postherpetic neuralgia: A review of therapeutic options. Journal of Pain and Symptom Management, 28(4), 396–411.

Baron, R. (2004). Post-herpetic neuralgia case study: Optimizing pain control. European Journal of Neurology, 11(Suppl. 1), 3–11.

Sabatowski, R., Galvez, R., Cherry, D., Jacquot, F., Vincent, E., Maisonobe, P., et al. (2004). Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: Results of a randomized, placebo-controlled clinical trial. Pain, 109, 26–33.

Stankus, S., Dlugopolski, M., & Packer, D. (2000). Management of herpes zoster (shingles) and post herpetic neuralgia. American Family Physician, 61, 2437–2444, 2447-2448. Retrieved April 23, 2005, from www.aafp.org/afp/20000415/2437.html

VZV Research Foundation. (n.d.). Post-herpetic neuralgia: Your questions answered. Retrieved April 25, 2005, from http://www.vzvfoundation.org/phn.html

Wounds are a source of pain, anxiety, and suffering for patients and their caregivers. Topical analgesics typically are indicated only for application to intact skin. An effective topical analgesic that could be applied to inflamed or open skin lesions would add greatly to the array of pain therapies. Local analgesia could decrease the need for systemic analgesics and, therefore, decrease the associated systemic side effects.

Background

Interest in topical morphine for use in painful wounds was spurred by the discovery of mu receptor activity in the peripheral nervous system. Peripheral opioid receptors are dormant in normal tissue but activate in minutes in response to inflammation.

Absorption of morphine is poor through intact epidermis and noninflamed tissue. Transdermal morphine applied to de-epithelialized skin has a bioavailability of about 75%. For transdermal morphine administration, the mean half-life is 7.5 ± 1.95 hours. The longer half-life accounts for the longer duration of effect of 12–24 hours for some patients.

Intrasite Gel^TM (Smith and Nephew Healthcare Division, Melbourne, Australia) is an aqueous gel that is used as a medium for morphine. When placed in contact with a wound, the gel absorbs excess exudate and produces a moist environment at the surface.

Study

In small case studies, topical application of morphine reduced the number of IV morphine doses required to control pain between dressing changes. This resulted in an overall reduction of opioid side effects from systemic administration of morphine. The University of Minnesota Medical Center’s inpatient pain consult service had been recommending the use of 0.1% morphine mixed in Intrasite Gel that is applied two to four times per day with dressing changes for a variety of wounds. A retrospective study of 36 patients during 18 months revealed that many patients with different kinds of painful wounds benefited from topical morphine. Patients ranged in age from five months to 84 years. The authors reviewed patients’ self-reported pain intensity scores and the amount of systemic analgesics used before and after the topical morphine applications.

Although the authors did not see statistically significant reductions in pain scores or systemic opioid doses, they found some very encouraging results. Fifty three percent of the patients in the study reported that their pain control was better because of the morphine Intrasite Gel. Another 19.4% reported improved pain control but were unsure whether the improvement could be attributed to the morphine gel or to other analgesic changes. Eighty percent of patients with pressure wound pain and 67% with stasis ulcer pain responded to the topical morphine treatment. About 50% of surgical wounds and other lesions responded to the treatment. Surprisingly, 56% of cases of cellulitis pain improved. Quotations from various charts included: “Reports pain controlled with morphine/Intrasite Gel for five to six hours.” “Morphine cream gave noticeable improvement, maybe 20%–30% relief.” “Morphine Intrasite Gel works instantly for pain site.”

Side Effects

Very few side effects have been reported in the literature regarding the use of transdermal morphine. Only two patients in the study complained of pruritus with application of the morphine gel. Intrasite Gel contains propylene glycol, which has been reported to be a potential irritant and sensitizing agent in a small number of patients. Intolerance to systemic morphine should not prohibit use of topical morphine.

Product Availability

No commercially manufactured product for morphine 0.1% in Intrasite Gel is available in the United States. Pharmacy compounded the gel as 1 mg preservative-free morphine sulfate per gram of Intrasite Gel. The product was dispensed in a multiple-dose plastic container. Storage of the product should be in a cool, dry place with an expiration date of two weeks.

Cost for 100 ml of the Compound

100 gm of Intrasite Gel costs approximately $30, and morphine 25 mg/ml X 4ml is $2.25. The dispensing container is $1.55. With labor estimated at $30, the total cost for about 10–20 doses is $64.

• Do not use in or around the eyes because the product is not suitable for such application.
• Do not use in wounds with excessive exudates or bleeding because the gel will not adhere to the wound surface.

Further Research

Future research is needed to examine the effects of morphine in Intrasite Gel on the healing trajectory of wounds. What is the typical duration of effect with different topical opioids? Is the amount of pain relief proportional to the amount of topical opioid used? Do specific characteristics of wounds or tissue damage influence the efficacy of topical opioids?

Conclusion

Morphine 0.1% in Intrasite Gel is an alternative method of providing pain relief for patients with a variety of wounds or inflamed skin. Topical application of morphine is limited to skin wounds or cellulitis because its absorption is poor through intact skin. The advantage of topical administration is increased efficacy of pain relief with minimal side effects. The use of topical morphine safely fills a niche in the treatment of painful wounds.