Pain
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Comparative Study
Transgene-mediated enkephalin release enhances the effect of morphine and evades tolerance to produce a sustained antiallodynic effect in neuropathic pain.
We examined the pharmacologic characteristics of herpes simplex virus (HSV) vector-mediated expression of proenkephalin in the dorsal root ganglion in a rodent model of neuropathic pain. We found that: (i). vector-mediated enkephalin produced an antiallodynic effect that was reversed by naloxone; (ii). vector-mediated enkephalin production in animals with spinal nerve ligation prevented the induction of c-fos expression in second order sensory neurons in the dorsal horn of spinal cord; (iii). the effect of vector-mediated enkephalin enhanced the effect of morphine, reducing the ED(50) of morphine 10-fold; (iv). animals did not develop tolerance to the continued production of vector-mediated enkephalin over a period of several weeks; and, (v). vector transduction continued to provide an analgesic effect despite the induction of tolerance to morphine. This is the first demonstration of gene transfer to provide an analgesic effect in neuropathic pain. The pharmacologic analysis demonstrates that transgene-mediated expression and local release of opioid peptides produce some effects that are distinct from peptide analogues delivered pharmacologically.
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Case Reports
Management of chronic intractable angina - spinal opioids offer an alternative therapy.
The successful treatment of chronic intractable angina by spinally administered opioids via an Algomed drug delivery device (hereinafter called the pump) is reported in seven patients. All patients had at least two prior cardiac surgeries and the duration of minimally controlled chronic intractable angina varied from 5 to 19 years prior to spinally administered opioids. ⋯ The opioid used was either morphine or fentanyl and the dose increase (either mg/year or microg/year, respectively) varied from 1.2 to 16. We suggest that bolus spinal morphine or fentanyl administered via the pump is a viable alternative for the effective control of angina when more established therapies have been found to provide insufficient pain relief.
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Comparative Study
Involvement of local cholecystokinin in the tolerance induced by morphine microinjections into the periaqueductal gray of rats.
The ventrolateral periaqueductal gray (PAG) is a key structure for the development of opioid tolerance. An increased activity of 'anti-opioids' like cholecystokinin (CCK) has been proposed as a possible mechanism for opioid tolerance. The present study evaluates the role of PAG-located CCK in the opioid tolerance induced by repeated microinjections of morphine (MOR) into PAG. ⋯ These results show that CCK has anti-opioid activity in PAG and that tolerance to MOR in PAG can be prevented or reversed if CCK receptors are blocked with PRO. Finally, opioid tolerance induced by repeated systemic MOR injections (5mg/kg intraperitoneal ) was reversed by a single microinjection of PRO into PAG. This emphasizes the central importance of PAG in the MOR/CCK interactions that lead to opioid tolerance.
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Comparative Study
'CatWalk' automated quantitative gait analysis as a novel method to assess mechanical allodynia in the rat; a comparison with von Frey testing.
A characteristic symptom of neuropathic pain is mechanical allodynia. In animal models of neuropathic pain, mechanical allodynia is often assessed using von Frey filaments. Although the forces applied with these filaments are highly reproducible, there are various disadvantages of using this method. ⋯ We demonstrate that these rats minimise contact with the affected paw during locomotion, as demonstrated by a reduction in stance phase and pressure applied during stance. Moreover, these parameters show a high degree of correlation with mechanical withdrawal thresholds as determined by von Frey filaments. We therefore suggest that the CatWalk method might serve as an additional tool in the investigation of mechanical allodynia.