Intrathecal ultra-low dose naloxone enhances the antihyperalgesic effects of morphine and attenuates tumor necrosis factor-α and tumor necrosis factor-α receptor 1 expression in the dorsal horn of rats with partial sciatic nerve transection.

BACKGROUND: Glutamate homeostasis and microglia activation play an important role in the development and maintenance of neuropathic pain. We designed this investigation to examine whether ultra-low dose naloxone administered alone or in combination with morphine could alter the concentration of the excitatory amino acids (EAAs) glutamate and aspartate, as well as the expression of tumor necrosis factor-α (TNF-α) and its receptors (TNFR1 and TNFR2) in the spinal cord dorsal horn of rats with partial sciatic nerve transection (PST). METHODS: Male Wistar rats underwent intrathecal catheter implantation for drug delivery and were divided in 7 groups: sham-operated + saline (sham), PST + saline (S), PST + 15 ng naloxone (n), PST + 15 µg naloxone (N), PST + 10 µg morphine (M), PST + 15 ng naloxone + 10 µg morphine (Mn), PST + 15 µg naloxone + 10 µg morphine (MN). Thermal withdrawal latency and mechanical withdrawal threshold, TNF-α and TNFR expression in the spinal cord and dorsal root ganglia, and EAAs glutamate and aspartate concentration in cerebrospinal fluid dialysates were measured. RESULTS: Ten days after PST, rats developed hyperalgesia (P < 0.0001) and allodynia (P < 0.0001), and increased TNF-α (P < 0.0001) and TNFR1 expression (P = 0.0009) were measured in the ipsilateral spinal cord dorsal horn. The antihyperalgesic and antiallodynic effects of morphine (10 µg) were abolished by high-dose naloxone (15 µg; P = 0.0031) but enhanced by ultra-low dose naloxone (15 ng; P = 0.0015), and this was associated with a reduction of TNF-α (P < 0.0001) and TNFR1 (P = 0.0009) expression in the spinal cord dorsal horn and EAAs concentration (glutamate: P = 0.0001; aspartate: P = 0.004) in cerebrospinal fluid dialysate. Analysis of variance (ANOVA) or Student t test with Bonferroni correction were used for statistical analysis. CONCLUSIONS: Ultra-low dose naloxone enhances the antihyperalgesia and antiallodynia effects of morphine in PST rats, possibly by reducing TNF-α and TNFR1 expression, and EAAs concentrations in the spinal dorsal horn. Ultra-low dose naloxone may be a useful adjuvant for increasing the analgesic effect of morphine in neuropathic pain conditions.

Neuroprotective effect of curcumin in an experimental rat model of subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) causes a high mortality rate and morbidity. It was suggested that oxidant stress plays an important role in neuronal injury after SAH. Therefore, we assessed the effect of curcumin on reducing cerebral vasospasm and neurologic injury in a SAH model in rat. METHODS: A double-hemorrhage model was used to induce SAH in rats. Groups of animals were treated with intraperitoneal injection of 20 mg/kg curcumin (curcumin group, n = 24) or dimethyl sulfoxide (vehicle group, n = 33), normal saline (SAH group, n = 34) or normal saline (sham group, n = 22), 3 h after SAH induction and daily for 6 days. Glutamate was measured before SAH induction and once daily for 7 days. Glutamate transporter-1, wall thickness and the perimeter of the basilar artery, neurologic scores, neuronal degeneration, malondialdehyde, superoxide dismutase, and catalase activities were assessed. RESULTS: Changes of glutamate levels were lower in the curcumin group versus the SAH and vehicle groups, especially on day 1 (56 folds attenuation vs. vehicle). Correspondingly, glutamate transporter-1 was preserved after SAH in curcumin-treated rats. In the hippocampus and the cortex, malondialdehyde was attenuated (30% and 50%, respectively). Superoxide dismutase (35% and 64%) and catalase (34% and 38%) activities were increased in the curcumin rats compared with the SAH rats. Mortality rate (relative risk: 0.59), wall thickness (30%) and perimeter (31%) of the basilar artery, neuron degeneration scores (39%), and neurologic scores (31%) were improved in curcumin-treated rats. CONCLUSIONS: Curcumin in multiple doses is effective against glutamate neurotoxicity and oxidative stress and improves the mortality rate in rats with SAH.

Intrathecal ultra-low dose naloxone enhances the antinociceptive effect of morphine by enhancing the reuptake of excitatory amino acids from the synaptic cleft in the spinal cord of partial sciatic nerve-transected rats.

BACKGROUND: In this study, we examined the effects of ultra-low dose naloxone on the antinociceptive effect of morphine and on spinal cord dorsal horn glutamate transporter expression in rats with neuropathic pain. METHODS: Neuropathic pain was induced in male Wistar rats by partial transection of the left sciatic nerve and an intrathecal catheter was implanted for drug administration; in some rats, an intrathecal microdialysis probe for cerebrospinal fluid (CSF) dialysate collection was also implanted. Nociception was assessed using the plantar test, a Hargreaves radiant heat apparatus, and by the von Frey test, using a dynamic plantar anesthesiometer. Glutamate transporter protein expression in the left spinal cord dorsal horn was examined by Western blotting and immunohistochemistry. Levels of the excitatory amino acids (EAAs) glutamate and aspartate in the CSF dialysate were measured using high-performance liquid chromatography. RESULTS: Reduced astrocyte expression of glutamate transporters (GLT-1 and GLAST levels were 55% and 53%, respectively, of that in sham-operated rats) in laminae I and II of the spinal cord dorsal horn ipsilateral to the partial sciatic nerve transection (PST), and hyperalgesia and allodynia in the PST hindlimb were observed. High-dose naloxone (15 µg) attenuated the antihyperalgesia and antiallodynia effects of the morphine (10 µg). In contrast, ultra-low dose (15 ng) naloxone enhanced the antinociceptive effect of morphine (10 µg), with an increase in the paw withdrawal threshold to thermal stimulus (from 19% to 35%) and to tactile stimulus (from 33% to 55%) compared with morphine treatment alone, and this was associated with restoration of GLAST and GLT-1 expression to control levels (102% and 114%, respectively) in the astrocytes of laminae I and II in the spinal cord dorsal horn ipsilateral to the PST hindlimb and a decrease in EAA levels in the CSF dialysate (glutamate: 10.0 µM; aspartate: 1.1 µM). CONCLUSIONS: Ultra-low dose naloxone enhanced the antinociceptive effect of morphine in PST rats, possibly by restoration of GLAST and GLT-1 expression in astrocytes, which inhibited the accumulation of EAAs in the synapses, resulting in a neuroprotective effect.

Collateral meridian acupressure therapy effectively relieves postregional anesthesia/analgesia backache.

Epidural and spinal aesthesia may cause backache. In fact, the overall incidence of postneuraxial block backache is 9% to 50% and the incidence of back pain on the third postoperative day ranges from 5.91% to 22% after spinal anesthesia. Five patients suffering from postneuraxial block backache after regional anesthesia or analgesia are reported. Despite administering conventional treatment modalities including bed rest, cold/warm packing, physical therapy, and medications with nonsteroidal anti-inflammatory drugs (NSAIDs), strong analgesics, and opioids, the backache persisted and disturbed the patients' daily life. Surprisingly, utilization of a new acupressure technique, collateral meridian acupressure therapy (CMAT), relieved the backache dramatically.

Shoulder tip pain after laparoscopic surgery analgesia by collateral meridian acupressure (shiatsu) therapy: a report of 2 cases.

OBJECTIVES: This article describes 2 cases of collateral meridian acupressure (shiatsu) therapy (CMAT) for treatment of shoulder tip pain after laparoscopic cholecystectomy (LC). Both cases showed marked pain relief with reduction of skin temperature (1 degrees C) of the affected shoulder after CMAT. CLINICAL FEATURES: A 32- and a 53-year-old female presented with right shoulder tip pain after LC surgery. The repeated dose of intravenous ketorolac 30 mg and meperidine 50 mg did not improve the pain. Because of persistent pain and episodes of nausea and vomiting after intravenous nonsteroidal anti-inflammatory drugs and opioid medications, patients refused to take more analgesics, and we were consulted for pain management. INTERVENTION AND OUTCOME: After informed written consent obtained, CMAT was performed using acupoints located on the contralateral (left) kidney meridian to treat affected (right) shoulder pain. Postoperatively, patients' pain intensity was measured using a numeric pain scale. The infrared thermography of shoulder tip was obtained before and after the CMAT. Both patients reported immediate pain relief after the CMAT, with pain scores decreased from 5 to 1 of 10 and 5 to 0 of 10, respectively. Moreover, the local skin temperature of affected shoulders were significantly decreased in both patients after the CMAT. Similarly, the temperature difference between patients' affected and nonpainful shoulders were also significant after the CMAT. CONCLUSION: The results of these 2 cases suggest that the CMAT may be effective in reducing patients' post-LC shoulder tip pain without medication. An associated reduction of skin temperature of the painful shoulder with CMAT warrants further investigation.