The role of spinal nitric oxide and glutamate in nociceptive behaviour evoked by high-dose intrathecal morphine in rats

Intrathecal analgesia has emerged as a key therapeutic option for pain relief for patients who have failed other treatment avenues as well as patients with adequate analgesia on high dose enteral or parenteral therapy but with unacceptable side effects. Intrethecal infusions of analgesics have been increasingly utilized since the later 1980s for the treatment of persistent pain. The purpose of this review is to provide research based clinical insight regarding the safe and appropriate use of the intrathecal infusion modality. Long-term intrathecal infusion analgesia or long-term intrathecal or long-term intrathecal analgesic therapy has significantly progressed over the past 25 years. The evidence for implantable intrathecal infusion systems is strong for short-term improvement in pain of malignancy or neuropathic pain. The evidence is moderate for long-term management of persistent pain. Reasonably strong evidence exists for the use of long-term intrathecal analgesic therapy in alleviation of cancer pain; however, the evidence supporting long-term efficacy in persistent noncancer pain is less convincing. Future studies are needed to better define the role of long-term intrathecal analgesic therapy in persistent pain, especially with respect to which pain conditions or subpopulations of patients are most responsive to ong-term intrathecal analgesic therapy, and which agents or combination of agents are most appropriate for which pain conditions or subpopulations of patients. Novel combinations of intrathecal analgesics such as clonidine and gabapentin deserve future study. The current body of literature supports the use of intrathecal agents for the treatment of moderate or severe pain related to cancer and noncancer origins. Further clinical studies are needed to evaluate the efficacy and safety of new intrathecal drugs, the complications related to these devices, and the proper selection of patients to receive these treatments. Key words: Intrathecal, morphine, baclofen, pump, implantable, infusion

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Role of nitric oxide in regulation of long-term pressure-natriuresis relationship in Dahl rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.6.h2375 ◽

1995 ◽

Vol 268 (6) ◽

pp. H2375-H2383 ◽

Cited By ~ 18

Author(s):

L. Hu ◽

R. D. Manning

Keyword(s):

Nitric Oxide ◽

Arterial Pressure ◽

Whole Body ◽

High Dose ◽

No Production ◽

High Sodium ◽

Induced Hypertension ◽

Pressure Natriuresis

The aim of this study was to determine the role of nitric oxide (NO) in the development of salt-induced hypertension in the Brookhaven strain of Dahl rats. Six- to seven-week-old conscious salt-sensitive (S) and salt-resistant (R) rats with indwelling arterial and venous catheters received low-, normal-, and high-sodium intakes sequentially over a 16-day period, and L-arginine was infused intravenously at 2 or 4 mg.kg-1.min-1 over this time. The S rats had an impaired NO production as evidenced by a decreased urinary nitrate plus nitrite excretion. The administration of the low or high dose of L-arginine increased the whole body NO production of the S rats to that of the control R rats, and the high dose of L-arginine prevented the shift of long-term pressure-natriuresis relationship, the elevation of arterial pressure, and the increase in salt sensitivity of arterial pressure in the S rats. The sodium and water balances were not different between the age-matched R and S rats. In conclusion, a continuous infusion of L-arginine prevented both the changes in the pressure-natriuresis relationship and the development of salt-induced hypertension in Dahl S rats.

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Role of atrial natriuretic peptide in controlling diabetic nephropathy in rats

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2017-0146 ◽

2018 ◽

Vol 29 (5) ◽

pp. 499-505 ◽

Cited By ~ 2

Author(s):

Lakhwinder Singh ◽

Atul Arya ◽

Sumeet Gupta

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Diabetic Nephropathy ◽

Low Dose ◽

Thiobarbituric Acid ◽

Urine Concentration ◽

High Dose ◽

Nitric Oxide Level ◽

Nitrite Nitrate

Abstract Background Diabetes is a downregulator of atrial natriuretic peptide (ANP), resulting in reduced nitric oxide level and low expression of endothelial nitric oxide synthase by which nitric oxide level get reduced. In the present study, we examined the role of ANP in reduced nitric oxide level, which may be responsible in controlling diabetic nephropathy in rats. Methods Serum nitrite/nitrate ratio, blood urea nitrogen, protein in urine, urinary output, serum creatinine, serum cholesterol, kidney weight, kidney hypertrophy, renal cortical collagen content, thiobarbituric acid level, and antioxidant enzymatic activities were assessed. Results Treatment with lisinopril (1 mg/kg) significantly attenuated diabetes-induced elevated glucose level, cholesterol level, and protein in urine concentration. Whereas ANP at low dose (5 μg/kg) has no effect on elevated markers of diabetic nephropathy, treatment with intermediate (10 μg/kg) and high-dose ANP (20 μg/kg) significantly attenuated the diabetes-induced increased blood urea nitrogen, protein in urine, urinary output, creatinine, cholesterol, kidney weight, kidney hypertrophy, renal collagen content, and thiobarbituric acid level and reduced endogenous antioxidant enzymatic activities. High dose of ANP was more effective in attenuating the diabetes-induced nephropathy, renal oxidative stress, and antioxidant enzyme activity as compared with the treatment with low-dose ANP (5 μg/kg), intermediate-dose ANP (10 μg/kg), or lisinopril (1 mg/kg, employed as standard agent). Administration of erythro-9-(2-hydroxy-3-nonyl)adenine, a phosphodiesterase-2 inhibitor (3 mg/kg), in combination with high-dose ANP significantly attenuated high-dose ANP induced ameliorative effects in diabetic nephropathy. Conclusions Taken together, these results indicate that diabetes-induced oxidative stress and lipid alterations may be responsible for the induction of nephropathy in diabetic rats. ANP at intermediate and high doses have prevented the development of diabetes-induced nephropathy by reducing the cholesterol level, protein in urine concentration, and renal oxidative stress and by increasing the nitrite/nitrate ratio, certainly providing the direct nephroprotective action.

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