Amyotrophic Lateral Sclerosis and Pain: A Narrative Review from Pain Assessment to Therapy.

Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2-5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease's stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients' satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients.

Therapy with autologous adipose-derived regenerative cells for the care of chronic ulcer of lower limbs in patients with peripheral arterial disease.

BACKGROUND: An ulcer is a trophic lesion with loss of tissue that often has a multifactorial genesis. It typically diverges from the physiologic processes of regeneration because it rarely tends to heal spontaneously. In this study, we used purified adipose-derived stem and regenerative cells (ADRCs) extracted from autologous fat, for the care of chronic ulcers of the lower limbs of arteriopathic patients. The primary objective of this study was complete re-epithelization of chronic ulcers; the secondary objective was a decrease in diameter and depth. METHODS: From January 2010 to January 2012, 20 patients with peripheral arterial disease, with an ankle-brachial index between 0.30-0.40, in the age range 60-70 y (14 men and six women), with chronic ulcers of the lower limb, were involved in the study. Only 10 arteriopathic patients (seven men and three women) with chronic ulcers of the lower limb were surgically treated. Using the Celution system, we isolated a solution of ADRCs in about 150 min. The isolated cells were injected through a 10-mL syringe into the edges of the ulcer, taking care to spread it in all directions. Using a small amount of Celution extract, we performed cell characterization by flow cytometry analysis and cell viability assay. RESULTS: We monitored patients treated with ADRC or untreated at 4, 10, 20, 60, and 90 d. In all cases treated with ADRC, we found a reduction in both diameter and depth of the ulcer, which led to a decrease in pain associated with the ulcer process. In six of 10 cases there was complete healing of the ulcer. Characterization of the cells by FACS clearly showed that the ADRC cells contained adipose-derived stem cells. Viability assays demonstrated that partial or total closure of the ulcer was attributable exclusively to ADRC cells present in the Celution extract, and not to growth factors extracted during the process of purification of the Celution and injected together with the cells. CONCLUSIONS: For the first time, the Celution method has been applied for the care of chronic ulcers in the lower extremity of patients with peripheral arterial disease. Our results demonstrate that the technique is feasible for autologous cell application and is not associated with adverse events. Moreover, the transplantation of autologous stem cells extracted with Celution may represent a valuable method for the treatment of chronic ulcers in lower limbs of arteriopathic patients.

Pregabalin and transcutaneous electrical nerve stimulation for postherpetic neuralgia treatment.

OBJECTIVE: Postherpetic neuralgia (PHN) is responsible for one of the most common types of neuropathic pain, described as a burning pain that shakes, hits, and tightens and includes allodynia and paresthesia. AIM OF THE STUDY: To evaluate the efficacy of Pregabalin when used during transcutaneous electric nerve stimulation (TENS) in patients with PHN and to analyze any changes in physical activity and sleep quality. METHODS: Patients aged 50 to 80 years were included in this randomized study. We enrolled 15 male (average age 65+/-8.6 y) and 15 female patients (average age 64+/-8.2 y). The male patients had a history of neuropathic pain lasting 15.6+/-8.8 months whereas the female patients had a history of neuropathic pain lasting about 14.9+/-8.6 months. We began with 1 week of patient screening followed by a week of Pregabalin titration. Then, we established the dose of Pregabalin for each patient to obtain visual analog scale (VAS) of less than 60 mm. The eligible patients were randomly divided into 2 groups receiving Pregabalin + TENS or Pregabalin+TENS placebo for the following 4 weeks. Patients underwent 8 outpatient visits during which they completed VAS, SF-McGill Pain Questionnaire, and sleep interference questionnaire. RESULTS: The resulting data showed that Pregabalin administration associated with TENS reduced pain in patients with PHN. At the end of the treatment, all the observed groups presented a reduction of mean VAS. The group treated with Pregabalin 300 (P300)+TENS had a reduction of pain of 30% and the group treated with Pregabalin 600 (P600)+TENS had a reduction of pain of 40%. The comparison between group P300+TENS versus group P300+TENS placebo showed a statistically significant reduction of VAS (P300+TENS 25+/-0.67 vs. P300+TENS placebo 39+/-1.19 P<0.02). Moreover, the comparison between group P600+TENS versus group P600+TENS placebo has shown a statistically significant reduction of VAS (P600+TENS 23+/-0.78 vs. P600+TENS placebo 32+/-0.81 P<0.02). At the end of the study, all groups showed a statistically significant difference in terms of sleep interference, Short-Form McGill Pain Questionnaire total score, and Short-Form McGill Pain Questionnaire Present Pain Intensity. CONCLUSIONS: These data support the conclusion that Pregabalin gives better results when combined with TENS therapy, which is an analgesic nonpharmacologic procedure. Therefore, a multidisciplinary treatment should be considered for this kind of pain.