[Effect of mild and strong manual acupuncture stimulation of "Huantiao" (GB 30) on mechanical pain thresholds and extracellular signal-regulated kinase protein expression in spinal dorsal horns in rats with neuropathic mirror-image pain].

OBJECTIVE: To observe the effect of different intensities of manual acupuncture (MA) stimulation on mechanical pain thresholds (PTs) and the expression of phosphorylated extracellular signal-regulated kinases (p-ERK) in lumbar spinal dorsal horn regions in rats with neuropathic mirror-image pain, so as to explore its mechanisms underlying analgesia. METHODS: Forty male SD rats were equally and randomly divided into control, spinal nerve ligation (SNL) model, mild MA-stimulation, and strong MA-stimulation groups. Neuropathological pain model was established by ligature of the spinal nerve (L 5). Three days after the SNL, bilateral "Huantiao" (GB 30) were stimulated by rotating the thin (0.22 mm x 13 mm) or thick (0.3 mm x 13 mm) filiform needles at a frequencies of 60 times/min or 180 times/min and at an angle of 180 degrees or 360 degrees for 2 min for rats in the mild and strong MA-stimulation groups, respectively, followed by remaining the needle in place for 30 min. The mechanical PTs were measured before and after SNL. The expression of p-ERK protein in bilateral dorsal horn regions of the lumbar spinal cord (L4- L 6) was detected by Western blot. RESULTS: In comparison with the control group, the mechanical PTs were significantly decreased beginning from the 3rd day on after SNL on the affected side and from the 7th day on after SNL on the healthy hindpaw (P < 0.05), simultaneously, p-ERK protein expression levels of dorsal horn regions on both sides of the spinal cord were considerably up-regulated on the 12th day (P < 0.05). Compared with the model group, the PTs of the affected hindpaw and the healthy hindpaw were significantly increased on the 7th and 12th day in the strong MA-stimulation group (P < 0.05, P < 0.01), whereas pERK expression levels in the bilateral spinal dorsal horn regions were obviously down-regulated in the strong MA-stimulation group (P < 0.05). No significant differences were found between the model and mild MA-stimulation groups in the PTs of bilateral hindpaws and p-ERK expression levels of the bilateral spinal dorsal horn regions (P > 0.05) except the PTs of the healthy hindpaw on 7th day (P < 0.05). CONCLUSION: Strong MA-stimulation can alleviate neuropathic mirror-image pain in SNL rats, which is closely related to its effect in down-regulating the expression of p-ERK in the bilateral spinal dorsal horn regions.

[Immediate analgesic effect of electroacupuncture and its regulation mechanism via spinal p-ERK1/2].

OBJECTIVE: To observe influence of electroacupuncture (EA) on phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in spinal cord dorsal horn (SCDH) in rats with acute inflammatory pain induced by complete Freund's adjuvant (CFA), further elucidate the immediate analgesic mechanism of EA via cellular signal transduction. METHODS: Fifty-three healthy male SD rats were divided into two batches. The inflammatory pain models of the first batch of 23 rats were established by using CFA. The changes of the paw withdrawal thresholds (PWTs) of rats were observed and positive cells of p-ERK1/2 in affected SCDH were detected by using immunohistochemistry method. The second batch of 30 rats were randomly divided into a blank control group (N group), CFA group and EA group, 10 rats in each group. The rats of CFA group and EA group were induced inflammatory pain by using CFA, and the EA group was treated with EA at 5.5 h after the model establishment. The changes of PWTs and the positive cells of p-ERK1/2 in SCDH were observed. RESULTS: The PWTs of the first batch of rats obviously decreased at 5 h, 3 d, 7 d and 14 d after CFA administration (all P< 0.01). However, the p-ERK1/2 positive cells in affected SCDH only increased at 5 h after CFA-injection and returned to normality at 3 d after the model establishment. In the second batch, compared with that of N group at the same time point, PWTs of rats in both CFA and EA group obviously decreased after the model establishment (both P<0.01). PWTs of rats in EA group which accepted EA treatment once were longer than those before EA treatment and corresponding PWTs in CFA group at the same time point (both P<0.01). Moreover, the numbers of p-ERK1/2 positive cells of affected SCDH increased significantly in CFA group at 6 h after the model establishment (P<0.01), however, which were decreased significantly in EA group (P<0.01). CONCLUSION: Inhibiting ERK1/2 activation of SCDH may be one of the pivotal mechanism of cellular signal transduction of the immediate analgesic effect educed by EA.

A prospective study of serum pseudocholinesterase levels in patients with chronic spinal pain: a preliminary study.

STUDY DESIGN: One-dimensional polyacrylamide gel electrophoresis was used to study serum esterase enzymatic activity in three groups of patients and one group of normal volunteers. OBJECTIVES: To determine whether there is a statistically significant correlation between variations of serum pseudocholinesterase and the perception of pain in patients with chronic spinal pain. SUMMARY OF BACKGROUND DATA: Changes in levels of cholinesterase in the extracellular space of the brain and in the cerebral spinal fluid have been found to be associated in animal pain experimentation. METHODS: Ninety-three surgical patients with chronic spinal pain, six surgical control subjects operated for conditions not associated with pain, 21 normal control volunteers, and nine disabled patients receiving monetary benefits were studied. The patients were analyzed for a period of time by rating the perception of their pain with a visual assessment score at the time venous blood was drawn. Serum samples were prepared, serum pseudocholinesterase was monitored, separated, and quantified according to Allen et al.5 Paired sample t tests were used to statistically evaluate the data. RESULTS: A trend of correlation was noted between preoperative serum pseudocholinesterase levels and visual assessment score: serum pseudocholinesterase levels increased as visual assessment score increased. The mean preoperative serum pseudocholinesterase level of chronic spinal pain patients (1313; SE = 26), which was significantly higher than the mean levels of the normal control volunteers (941; SE = 24; P<0.001) and that of surgical control subjects (1018; SE = 63; P <0.01), decreased significantly with anesthesia (P<0.005). The mean preoperative serum pseudocholinesterase level of the surgical controls, however, remained unchanged with anesthesia. A correlation demonstrated between visual assessment score and serum pseudocholinesterase in chronic spinal pain patients was not observed in six of nine patients receiving disability payments for more than a year. CONCLUSIONS: Measurements of quantitative alterations of serum pseudocholinesterase levels may be useful in the treatment of patients with chronic spinal pain.

Adverse drug reactions and debrisoquine/sparteine (P450IID6) polymorphism in patients with fibromyalgia.

OBJECTIVE: To assess the frequency of adverse drug reaction in patients with fibromyalgia in relation to medications prescribed for this condition. To evaluate the potential role of the P450IID6 phenotype in the pathogenesis of these adverse drug reactions. METHODS: Thirty-five patients with fibromyalgia were assessed using a structured questionnaire with demographic and clinical data and perceived adverse drug reactions. A sample of 60 patients with rheumatoid arthritis and 62 patients with localized back pain served as controls. The P450IID6 phenotype was determined for each of the fibromyalgia patients. RESULTS: Overall, 141 patients had used NSAID and 79 (56%) of them reported adverse effects. Antidepressant drugs were used by 68 patients and 35 (51%) patients had adverse effects. Muscle relaxant drugs were used by 48 patients and 15 (31%) of them reported side effects. Analgesics were used by 122 patients and 22 (18%) had experienced adverse effects. Statistical differences in the frequency of adverse effects were found with antidepressant drugs in the fibromyalgia group, compared with rheumatoid arthritis (p=0.01) and back pain (p=0.02). Four of the 35 patients (11.4%) had a metabolic ratio (M.R.) greater than 0.30 (log M.R.= -0.52) indicative of the poor metabolizers (PM) phenotype. M.R. varied from 0.005 (log M.R. = -2.30) to 4.99 (log M.R. = 0.70). CONCLUSIONS: The problem of adverse drug reactions in fibromyalgia patients does not appear to correlate with the PM phenotype of the P450IID6 oxidative enzyme. It also is unlikely that altered xenobiotic detoxification attributable to this PM phenotype would have a significant role in the development of fibromyalgia.

Collagenase: an experimental study of intervertebral disc dissolution.

This study reports the use of a purified form of the enzyme collagenase (Nucleolysin) to effect dissolution of the normal nucleus pulposus in a series of dogs and monkeys. A consistent dissolution effect has been observed. The toxicity of the enzyme to surrounding local tissues has been studied in the same species with an indication of safety in all areas other than intrathecal administration. A margin of safety in intrathecal administration between the effective dose and toxic dose has been suggested in the monkey. Mice LD50 studies and systemic toxicity studies in dogs show a satisfactory margin of safety for this enzyme. Guinea pig studies show no significant antigenicity.

[The diagnostic value of enzymes in cerebrospinal fluid (author's transl)]. / Der diagnostische Wert von Enzymbestimmungen im Liquor cerebrospinalis

The clinical value of enzyme activities in cerebrospinal fluid (CSF) should be proved by examination of GOT, GPT, LDH and CPK in blood and CSF of 115 unselected and 4 selected patients. Only the GOT showed a significant correlated increase in diffuse vascular diseases in both, serum and CSF. Discussing the literature the authors affirm, that only mechanical or functional lesion of the blood-brain-barrier will increase the enzyme activities in serum and CSF. The origin of these enzymes however is unknown till now.