Long-term Inhibition of Soleus H-reflex with Epidural Adhesiolysis and Pulsed Radiofrequency in Lumbosacral Neuropathic Pain.

INTRODUCTION: Scientific data about neurophysiological changes subsequent to pulsed radiofrequency (PRF) are still lacking. The goal of this study was to evaluate sural nerve conduction and Hoffmann reflex (H-reflex) in soleus muscle following adhesiolysis and PRF in patients with unilateral chronic lumbosacral L5-S1 neuropathic radiating pain. METHODS: Seventeen patients received two cycles of 240 seconds high-voltage PRF and epidural adhesiolysis. Sural nerve action potential (SNAP) and the ratio of maximum H-reflex to maximum M response (H/M ratio) as well as pain scores were collected in both lower limbs before, immediately following, and 1 month after the treatment. RESULTS: At follow-up, a significant reduction in numeric rating scale (NRS) and Douleur Neuropathique 4 Questions (DN4) scores was observed in 53% of patients reporting pain improvement of ≥ 30% over baseline. The H/M ratio was decreased in the affected limb following PRF (P = 0.01) and 1 month after the treatment (P = 0.04). A direct correlation was observed between H/M ratio variation and NRS score at follow-up in the treated limb (P = 0.04). No significant difference in sural nerve latency, amplitude, and velocity was detected between affected and normal side after treatment and at follow-up. CONCLUSIONS: Epidural adhesiolysis and PRF of the dorsal root ganglion seem to significantly affect spinal reflexes in patients with lumbosacral neuropathic radiating pain.

Electrocatheter-mediated High-voltage Pulsed Radiofrequency of the Dorsal Root Ganglion in the Treatment of Chronic Lumbosacral Neuropathic Pain: A Randomized Controlled Study.

OBJECTIVES: Despite the interest in scientific community, there is still poor evidence about pulsed radiofrequency (PRF) efficacy in the treatment of neuropathic pain. In order to determine whether high-voltage PRF and epidural adhesiolysis (PRF-EA) showed better results than epidural adhesiolysis alone (EA), a randomized, double-blind, comparative-effectiveness study was conducted in patients with chronic lumbosacral radiating pain and neuropathic features. MATERIALS AND METHODS: A total of 41 patients were randomly allocated to 2 groups. Twenty-one patients were randomized to receive 2 cycles of 240 seconds high-voltage PRF followed by the injection of local anesthetics, hyaluronidase, and betamethasone, whereas 20 patients underwent sham stimulation followed by adhesiolysis. The treatment was delivered at the affected lumbosacral roots and patients, treating physicians and assessors were blinded to intervention. RESULTS: A significant reduction of radiating pain was observed in mean Numeric Rating Scale score at follow-up. A change of -3.43 versus -1.75 (P=0.031) after 1 month and -3.34 versus -0.80 (P=0.005) after 6 months was reported in patients undergoing PRF-EA in comparison with EA, respectively. After 1 month, 57% of patients in the PRF-EA group experienced a pain reduction of ≥50% versus only 25% of patients allocated to EA (P=0.037). Improvement decreased to 48% in the PRF-EA group whereas only 10% of EA reported significant pain relief after 6 months (P=0.008). DISCUSSION: High-voltage PRF of dorsal root ganglion delivered through multifunctional electrode provided significant pain relief and may be considered a valuable treatment in chronic lumbosacral radicular pain with neuropathic features.

Interventional treatment for neuropathic pain due to combined cervical radiculopathy and carpal tunnel syndrome: a case report.

The coexistence of median and cervical nerve root damage might hide a complex pathophysiology. Here, we describe and discuss the case of a patient suffering from numbness and painful tingling of the hand, whose symptoms were effectively treated with pulsed radiofrequency and epidural administration of bupivacaine and morphine.

Combined epidural morphine and bupivacaine in the treatment of lumbosacral radicular neuropathic pain: a noncontrolled prospective study.

OBJECTIVE: The aim of this study was to investigate the therapeutic effectiveness of epidural morphine and bupivacaine in patients with chronic lumbosacral radicular neuropathic pain after the cessation of treatment. METHODS: Twenty-two patients with chronic lumbosacral pain with neuropathic features were enrolled. An indwelling catheter was placed into the epidural space, and each patient received an epidural injection of morphine chlorhydrate and bupivacaine up to three times a day. The medication was administered for 4 weeks. The pain intensity score on a 0-10 numeric rating scale (NRS), the total pain rating index rank (PRIr-T), and its coefficients were evaluated before treatment and 1 month after catheter removal. P-value <0.05 was considered statistically significant. RESULTS: NRS and PRIr-T were significantly reduced at follow-up (P=0.001 and P=0.03, respectively), whereas the parallel evolution of the two scores (r=0.75 and P<0.001, respectively) confirmed significant pain relief lasting up to 1 month after treatment cessation. None of the four pain rating coefficients was significantly modified compared to the others in either responders or nonresponders. Successful clinical outcome (pain reduction >30% in NRS) was reached and maintained in half of the patients at follow-up. CONCLUSION: Combined epidural morphine and bupivacaine seems to be effective in the treatment of neuropathic pain.

Effectiveness of pulsed radiofrequency with multifunctional epidural electrode in chronic lumbosacral radicular pain with neuropathic features.

BACKGROUND: Lumbosacral radicular pain is a common clinical finding with a statistical prevalence ranging from 9.9% to 25% in the general population. OBJECTIVE: To investigate the effectiveness of dorsal root ganglion pulsed radiofrequency (PRF) in patients with chronic lumbosacral radicular pain and neuropathic features. STUDY DESIGN: Prospective case series clinical outcome study. METHODS: We evaluated 34 patients with lumbosacral neuropathic pain who underwent PRF at the corresponding level of radicular symptoms distribution (ranging from L3 to S1). Each patient suffered a single leg-radiating pain with probable neuropathic features (assessed with clinical grading) lasting for > 6 months and unresponsive to previous treatments. A multifunctional PASHA-electrode® was introduced with trans-sacral access through a hollow needle, placed under fluoroscopic guidance into the lumbosacral epidural space and its active tip moved close to the dorsal root ganglion responsible of the clinical symptoms. After connecting the electrode to a generator, stimulation tests were performed and PRF was started and applied for 240 seconds at a frequency of 2Hz, amplitude of 45 V and a tip temperature between 40 - 42°C. If the pain involved more than a single nerve root, the electrode was placed at a different segment and the procedure repeated. Outcome measures included the pain intensity score on a 0 - 10 numeric rating scale (NRS) and the Italian Pain Questionnaire (QUID) at pre-treatment, one and 6 months post-treatment. P values < 0.05 were considered statistically significant. RESULTS: In comparison with pre-treatment, a significant reduction in pain score was observed in mean NRS either at one and 6 months (P < 0.001). The QUID - Pain Rating Index rank displayed a parallel trend at the first (P < 0.001) and last follow-up (P = 0.01). Moreover, a direct correlation between the 2 scales occurred, showing a parallel score decreasing (P < 0.001). Eighteen (52.9%) and 17 (50%) of 34 patients showed pain reduction in NRS > 2 points and > 30%, at one and 6 months, respectively. LIMITATIONS: The non-controlled design of the study, the patients were heterogeneous, the small number of patients, and the duration of follow-up was limited to 6 months. CONCLUSIONS: PRF of dorsal root ganglion performed with a multifunctional electrode for > 240 seconds appears to be safe and might be more effective than the classic 120 seconds needle-mediated approach. Therefore, it may be considered as a valuable tool for the treatment of lumbosacral radicular pain with neuropathic features.

Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients.

BACKGROUND: In male patients suffering from chronic pain, opioid administration induces severe hypogonadism, leading to impaired physical and psychological conditions such as fatigue, anaemia and depression. Hormone replacement therapy is rarely considered for these hypogonadic patients, notwithstanding the various pharmacological solutions available. METHODS: To treat hypogonadism and to evaluate the consequent endocrine, physical and psychological changes in male chronic pain patients treated with morphine (epidural route), we tested the administration of testosterone via a gel formulation for one year. Hormonal (total testosterone, estradiol, free testosterone, DHT, cortisol), pain (VAS and other pain questionnaires), andrological (Ageing Males' Symptoms Scale-AMS) and psychological (POMS, CES-D and SF-36) parameters were evaluated at baseline (T0) and after 3, 6 and 12 months (T3, T6, T12 respectively). RESULTS: The daily administration of testosterone increased total and free testosterone and DHT at T3, and the levels remained high until T12. Pain rating indexes (QUID) progressively improved from T3 to T12 while the other pain parameters (VAS, Area%) remained unchanged. The AMS sexual dimension and SF-36 Mental Index displayed a significant improvement over time. CONCLUSIONS: In conclusion, our results suggest that a constant, long-term supply of testosterone can induce a general improvement of the male chronic pain patient's quality of life, an important clinical aspect of pain management.

Endocrine consequences of opioid therapy.

Gonadal hormones are known to be affected by morphine and other opioids. In this paper, we summarize data collected in recent years which clearly indicate that the opioid-induced effects on steroid hormones depend on the opioid used and in some cases on the sex of the subject. Indeed morphine is able to reduce hormones like testosterone and cortisol in both male and female subjects in just a few hours, probably acting directly on peripheral glands. These depressant effects of morphine on hormones are also present in the treatment of surgical pain and are quickly reversible once opioid administration is suspended. Similar actions were also found to occur in experimental animals and in vitro in glial cells, further confirming the morphine-induced reduction of testosterone cell content. Testosterone and its metabolites are well known substances involved in the development and maintenance of the brain and all body structures. Thus when treating pain with opioids, their effects on hypothalamo-pituitary-gonadal and hypothalamo-pituitary-adrenal-related hormones must be considered and, where possible, hormone replacement therapy should be started.

Gender-related effects of chronic non-malignant pain and opioid therapy on plasma levels of macrophage migration inhibitory factor (MIF).

Macrophage migration inhibitory factor (MIF) is a cytokine produced by neuroendocrine and immune tissues that possesses several characteristics of a neuroendocrine mediator. Chronic pain is known to affect and to be affected by neuroendocrine and immune mechanisms. In the present study, the plasma levels of MIF and several hormones (cortisol, estradiol, testosterone) were determined to evaluate their mutual behaviour in controls and in chronic pain patients. Blood samples were collected from males and females divided into groups depending on their age (younger or older than 55) and health condition: (1) pain-free control subjects; (2) chronic non-malignant pain subjects. Moreover, two additional groups were added to evaluate the effects of short- and long-term opioid administration: (3) short-term opioid-treated chronic pain patients and (4) long-term opioid-treated chronic pain patients (longer than 6 months). MIF in control/younger men was higher than in all the other control and chronic pain groups. MIF was lower in pain patients than in controls of both sexes. MIF was not changed by morphine administration; its levels remained lower in opioid-treated subjects than in controls after both short- and long-lasting administration. Chronic pain changed hormone plasma levels differently in male and female patients. MIF was positively correlated with testosterone and negatively with estradiol. These results demonstrate sex differences in the younger men and women and a strong pain-induced decrease of MIF availability. These findings suggest the involvement of this cytokine in the sex differences observed in chronic pain conditions.