Oral morphine induces spinal 5-hydroxytryptamine (5-HT) release using an opioid receptor-independent mechanism.

Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of the spinal 5-HT release induced by morphine are not well understood. The purpose of this study was to define the role and mechanism of spinal 5-HT release induced by oral morphine. We also examined whether persistent pain affected the spinal 5-HT release induced by oral morphine. Spinal 5-HT release was measured using microdialysis of lumbar cerebrospinal fluid (CSF). Two opioids, morphine and oxycodone, were orally administered and 5-HT release was measured in awake rats. Naloxone and ß-funaltrexamine (ß-FNA) were used to determine whether the effect of morphine on 5-HT release was mediated by opioid receptor activation. To study persistent pain, a formalin test was used. At 45 min after oral morphine administration, the formalin test was started and spinal 5-HT release was measured. Oral morphine, but not oral oxycodone, increased 5-HT release at the spinal cord to approximately 4000% of the baseline value. This effect of morphine was not antagonized by either naloxone or ß-FNA at a dose that antagonized the antinociceptive effect of morphine. Formalin-induced persistent pain itself had no effect on spinal 5-HT release but enhanced the oral morphine-induced spinal 5-HT release. Oral morphine-induced spinal 5-HT release was not mediated by opioid receptor activation. Spinal 5-HT induced by oral morphine did not play a major role in the antinociceptive effect of morphine in the hot plate test. Persistent pain increased oral morphine-induced spinal 5-HT release.

Oral acetaminophen-induced spinal 5-hydroxytriyptamine release produces analgesic effects in the rat formalin test.

The mechanism by which acetaminophen produces its analgesic effects is not fully understood. One possible mechanism is the activation of the spinal 5-hydroxytryptamine (5-HT) receptor, although direct evidence of spinal 5-HT release has not yet been reported. N-arachidonoylphenolamine (AM404), a metabolite of acetaminophen, is believed to be the key substance that contributes to the analgesic effects of acetaminophen. In this study, we examined whether acetaminophen and AM404 induce spinal 5-HT release and the mechanism through which spinal 5-HT receptor activation exerts analgesic effects in a rat formalin test in an inflammatory pain model. Spinal 5-HT release was examined by intrathecal microdialysis in conscious and freely moving rats. Acetaminophen was administered orally, and AM404 was administered intracerebroventricularly. In rat formalin tests, oral acetaminophen and intracerebroventricular AM404 induced significant spinal 5-HT release and produced analgesic effects. The analgesic effect of oral acetaminophen was partially antagonized by intrathecal administration of WAY100135 (a 5-HT1A receptor antagonist) and SB269970 (a 5-HT7 receptor antagonist). In contrast, the analgesic effect of intracerebroventricular AM404 was completely antagonized by WAY100135, while SB269970 had no effect. Our data suggest that while oral acetaminophen and intracerebroventricular AM404 activate the spinal 5-HT system, the role of the spinal 5-HT system activated by oral acetaminophen differs from that activated by intracerebroventricular AM404.

Analgesic characteristics of a newly developed α2δ ligand, mirogabalin, on inflammatory pain.

Mirogabalin is a novel α2δ ligand approved in Japan for the treatment of peripheral neuropathic pain. However, the sites of action of α2δ ligands to produce analgesic effects on inflammatory pain remain unclear. In this study, we investigated the analgesic effect and site of action of mirogabalin using the rat formalin test, an acute inflammatory pain model. Mirogabalin was administered orally, intrathecally, and intracerebroventricularly. Open field tests were performed to evaluate the effect of oral-, intrathecally, and intracerebroventricularly administered mirogabalin on locomotor activity and orientation ability. Oral mirogabalin produced an analgesic effect when the formalin test was performed 4 h, but not 1 or 2 h, after oral administration. Intrathecal, but not intracerebroventricular, administration of mirogabalin produced analgesic effects when mirogabalin was administered 10 min before formalin injection. These analgesic effects were not antagonized by idazoxan, an α2 adrenergic antagonist; WAY100135, a 5-HT1A antagonist; or naloxone, an opioid receptor antagonist. Mirogabalin attenuated moving distances 1 and 2 h after oral administration and 10 min after intracerebroventricular administration, but not 10 min after intrathecal administration. In the oral administration group, the time course of the analgesic effect was different from that of moving distance. In the intracerebroventricular group, mirogabalin attenuated moving distances but did not produce an analgesic effect. In the intrathecal group, mirogabalin produced an analgesic effect but did not affect moving distances. These findings suggest that the analgesic effect of mirogabalin on the rat formalin test is mediated by spinal action and not by the activation of α2, 5-HT1A, or opioid receptors, and that the inhibitory effect of mirogabalin on moving distances is mediated by the supraspinal brain.

[Effective Use of Combination of Ultrasound-guided Femoral Nerve Block and Lateral Femoral Cutaneous Nerve Block for Harvesting Skin Grafts: Three Case Reports].

The pain of skin graft site after surgery is compara- tively severe. We present three cases of combined of ultrasound-guided femoral nerve block and lateral fem- oral cutaneous nerve block that was effective for har- vesting skin grafts. Case 1 : a 32-year-old man had a split-thickness skin grafting of lateral upper arm harvested from outside of the thigh under general anesthesia, brachial nerve block, femoral nerve block and lateral femoral cutane- ous nerve block. Case 2 : a 39-year-old man had split-thickness skin grafting of lower thigh harvested from outside of the thigh under general anesthesia, femoral nerve block and lateral femoral cutaneous nerve block. Case 3 : a 94-year-old man had split-thickness skin grafting of acrotarsium harvested from outside of the thigh under spinal anesthesia, femoral nerve block, lat- eral femoral cutaneous nerve block and sciatic nerve block. In all cases, there was no pain just after surgery, and postoperative pain was controlled well through the hospitalization with administration of oral analgesic agents.

[A case of malignant psoas syndrome diagnosed while treating sciatica].

While attempting to treat a 71-year-old male patient who had been diagnosed with sciatica from spinal canal stenosis, we discovered his prior cancer metastasizing to the psoas. We initially administered epidural block to him after confirming his prior rectal cancer had not metastasized to lumbar vertebral bones, but the block did not satisfactorily alleviate his pain, and he had difficulty stretching his lower limbs. CT scan to re-examine the cause revealed a metastasized cancer in the psoas. From this experience, we believe malignant psoas syndrome should be considered in addition to metastasis to lumbar vertebral bones, when evaluating lower back to lower limb pain in patients with previous cancer history.

[Effect of the sacroiliac ligament block on intractable low back pain in elderly patients].

BACKGROUND: Lumbar spine disease in the elderly people is complicated by a variety of pathophysiology in the spine and the cause of the pain is unclear. Diagnosis of pain may be difficult in patients with pain in the thigh and groin area. Sacroiliac joint is supporting the trunk and movable joint. We examined the effect of the sacroiliac joint block for intractable low back pain. METHODS: Retrospectively we examined the duration of disease in patients with hip and leg pain visiting the hospital for eight months, and we questioned the site of pain awareness. Newton test, Gaenslen test, Patrick test and Fadire test were carried out for sacroiliac joint pain in patients with at least one positive finding. When performing sacroiliac ligaments block local anesthetics was injected to check the position of the dorsal sacroiliac ligaments under ultrasonic echo whenever possible. The block is performed with the patients prone at a point one finger from the posterior superior iliac spine level at an angle of 30-45 degrees downward toward the outside. Injecting the drugs penetrating the ligament continued to give a feel slightly outward to avoid the iliac Cattelan 23 G needle. We confirmed pain assessment NRS at 11 (0-10), and the improvement of pain was assessed with the change of the NRS on the next return. RESULTS: NRS showed a significant decrease at all points in time before block, their pain decreased gradually. The patients showed NRS improvement of more than 50% of the first block in 15 of 24 patients. CONCLUSIONS: Block at the posterior sacroiliac ligament region significantly reduced pain for chronic intractable low back pain. The block was shown to be effective as a treatment and for diagnosis.

[Development and evaluation of a patient-reported outcome measure of pain-related sleep disturbances for pain clinic patients].

BACKGROUND: The purpose of this study was to develop a new tool, the Pain Sleep questionnaire, consisting of 20 items (PS-20) for measuring pain-related sleep disturbances in pain clinic patients, and to examine its reliability and validity. METHODS: The internal consistency, criterion validity compared with the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36v2), and construct validity of the PS-20 were tested. RESULTS: A total of 125 patients participated in this study. Cronbach's alpha coefficient was 0.969, indicating good internal consistency. The PS-20 score correlated moderately with the physical component summary of SF-36v2 and correlated weakly with the mental component summary of SF-36v2. From the graphical model using the Akaike information criterion and the Categorical principal component analysis, the items were divided into four domains: physical pain, trouble falling asleep, awakened by pain, and general health problems. CONCLUSIONS: The PS-20 was shown to be a valid and reliable questionnaire scale for measuring pain-related sleep disturbances among pain clinic patients.

Efficacy of limited-duration spinal cord stimulation for subacute postherpetic neuralgia.

Excellent outcomes were achieved with spinal cord stimulation (SCS) for 7 to 10 days on 2 patients who developed postherpetic neuralgia. Both patients were within 2 to 3 months of the onset of the condition, and nerve blocks provided only temporary pain relief and drug therapies had poor efficacy. The authors believe that limited-duration SCS for subacute postherpetic neuralgia is a useful treatment approach that may prevent the pain from progressing to chronic postherpetic neuralgia.