Analgesic effects of antidepressants alone and after their local co-administration with morphine in a rat model of neuropathic pain

Abstract

(2014) 'Analgesic eects of antidepressants alone and after their local co-administration with morphine in a rat model of neuropathic pain.', Pharmacological reports., 66 (3). pp. 459-465. Further information on publisher's website: Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. IntroductionNeuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system [1]. The most frequent etiologic factors of neuropathic pain are trauma (including post-surgery scars), metabolic disturbances (e.g., diabetes mellitus) and ischemia. The pathological mechanism of neuropathic pain differs significantly from that of inflammatory pain; studies have shown that the changes in spinal gene expression under neuropathy and inflammations are different [2]. Thus, the response to antinociceptive drugs, especially opioids, is not the same. It has generally been accepted that neuropathic pain is somewhat resistant to morphine administration in clinical studies [3,4], and the reduced ability of morphine to attenuate allodynia and hyperalgesia in experimental models of neuropathic pain has been demonstrated [5][6][7][8]. For these reasons, it is a common clinical practice to use analgesic drug combinations. The primary approach to treat neuropathic pain is the use of coanalgesics such as tricyclic antidepressants (TCA); however, their systemic application is associated with significant side effects, which can hinder the desired analgesic effect. An alternative approach to this is the topical administration of analgesics. Currently, the possibility of the topical Background:The therapy of neuropathic pain may include the use of co-analgesics, such as antidepressants, however, their desired analgesic effect is associated with significant side effects. An alternative approach to this is their local administration which has been proposed, but there is little data regarding their local co-administration with morphine and the nature of the interaction between morphine and either doxepin or venlafaxine, two antidepressant drugs that have been recently used in neuropathic pain therapies. Methods: This study was performed on rats after chronic constriction injury (CCI) to the sciatic nerve. The von Frey and Hargreaves' tests were used to assess mechanical allodynia and thermal hyperalgesia, respectively, after intraplantar (ipl) or subcutaneous (sc) administration of amitriptyline, doxepin, or venlafaxine, or their ipl co-administration with morphine on day 12-16 after inj...

Impact of migraine on fibromyalgia symptoms

“…The first phase of the investigation shows firstly that the co-occurrence of both conditions involves a higher level of generalized hypersensitivity to pain at somatic level with respect to migraine only and fibromyalgia only, as testified by significantly lower pain thresholds in both painful and control areas. All FMS, but not non-FMS, patients were under stable basal amitriptyline treatment; though in very low doses, this treatment could have potentially influenced pain sensitivity in FMS, by increasing the pain threshold [ 35 , 42 ]. However, even in this case, the outcome here found of a higher pain sensitivity in FMS vs non-FMS would not have changed without treatment; in contrast, the hypersensitivity difference would probably have been more pronounced.…”

“…Further antidepressants were excluded since all patients were already under amitriptyline treatment. Among calcium-channel blockers, flunarizine was chosen as, according to guidelines, it represents the molecule with the highest level of evidence of efficacy [ 35 – 37 ].…”

Effects of μ-Opioid Receptor Agonists in Assays of Acute Pain-Stimulated and Pain-Depressed Behavior in Male Rats: Role of μ-Agonist Efficacy and Noxious Stimulus Intensity

“…assays of acid-stimulated stretching in rats and mice (Cowan et al, 1977;Fürst, 1991;Stevenson et al, 2006;Pereira Do Carmo et al, 2009). Previous studies have also shown that m-opioid agonists block other examples of pain-stimulated behavior, such as tail-or paw-withdrawal responses from noxious thermal stimuli Holtzman, 1991, 1992;Gringauz et al, 2001;Taracha et al, 2009) or withdrawal responses in subjects rendered hypersensitive to thermal or mechanical stimuli by inflammatory or neuropathic manipulations (Wang et al, 2006;Cobos et al, 2012;Jagla et al, 2014). m-Agonist effects on pain-stimulated behaviors are often interpreted as evidence consistent with clinical analgesic efficacy .…”

Evaluation of central and peripheral analgesic activity of amitriptyline in mice

“…This signifies that amitriptyline showed analgesic activity mainly through central analgesic mechanism which is similar to the results found in previous studies. [24][25][26][27] In authors study we also found that amitriptyline showing analgesic activity through peripheral mechanism as evidenced by decrease in number of writhes in mice, although this decrement was not as good as diclofenac. But authors can't completely disagree with this fact that it partially improved pain through peripheral mechanism also.…”