Nociceptive threshold and analgesic response to morphine in aged and young adult rats as determined by thermal radiation and intracerebral electrical stimulation

ArticleinPharmacology Biochemistry and Behavior 84(1):148-57 · June 2006with6 Reads
DOI: 10.1016/j.pbb.2006.04.021 · Source: PubMed
The present experiment compared the nociceptive threshold and analgesic response to morphine in young (4-5 months) and aged (24 months) rats using peripheral thermal stimulation and intracerebral electrical stimulation. Responses to thermal stimuli were assessed using both the classical tail-flick procedure in which latency of response is the dependent variable and a new method in which threshold in calories of heat is the dependent variable. In the intracerebral nociceptive threshold procedure, electrical stimuli were delivered via an electrode implanted in the mesencephalic reticular formation (MRF), a pain pathway, and the animals were trained to terminate the stimulation by turning a cylindrical manipulandum embedded in one wall of the experimental chamber. For the classical tail-flick method, the aged rats required a greater intensity of stimulation to produce a basal response latency that was between 2.5 and 3.5 s. Using the new psychophysical method for determining the tail-flick threshold, the aged rats' basal thresholds were significantly higher than that of the young rats. However, the basal thresholds obtained by direct stimulation of the MRF failed to show a significant age effect, suggesting that the registration of pain is not different between young and aged rats. These age-related differences in baseline tail-flick response may be due to changes in the spinal reflex associated with aging. Although, there was no difference in the analgesic effects of morphine between young and aged rats using the latency of the tail-flick response, evidence for decreased analgesic response was seen using the tail-flick threshold measure and the intracerebral stimulation threshold method.
    • "The effect of aging on pain sensitivity and threshold is not well defined (Harkins et al. 1994). Some animals studies have indicated that reactivity to pain decreased in 25 month-old rats compared to 3 month-old animals either in response to thermal and mechanical stimuli (Akunne and Soliman 1994) or to thermal and electrical stimuli (Crosby et al. 2006). On the other hand, Islam et al. (1993) reported an enhanced nociception in 12, 18 and 24 month-old rats compared to 6 month-old rats; while Crisp et al. (1994) have shown that pain reactivity is enhanced in 25 monthold rats when compared to 15 month-old rats but not to 6 month-old rats. "
    [Show abstract] [Hide abstract] ABSTRACT: The effect of age on pain response to paw pressure and intraplantar formalin injection in rats is elucidated. Pain responses evoked by mechanical pressure on hind paw and intraplantar injection of formaldehyde (5%) into the hind paw were evaluated in groups of adult, young and aged male Sprague Dawley rats, after intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) injection of L-arginine or NG-nitro-L-arginine methyl ester (L-NAME). Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining was done in the two groups. The results show that pain response was reduced in the aged rats and enhanced pain response to paw pressure in aged rats only. L-arginine (i.c.v.) had no effect on pain response to paw pressure in the two groups but enhanced biphasic pain response to formalin. L-NAME (i.p. and i.c.v.) suppressed pain response to paw pressure in the two groups. L-NAME (i.c.v.) suppressed pain response to formalin during the acute phase and enhanced it during the late phase. NADPH-diaphorase activity was significantly greater in young rats. In conclusion, pain response is blunted in the aged rats. NO might be involved in mechanical nociception in aged rats and in formalin-induced nociception in both groups. NO blockade has an antinociceptive effect on pain response. Central NO has dual role in pain response evoked by formalin.
    Full-text · Article · Jun 2012
    • "The specific hypothesis of this investigation was that activation of the brain reward pathway would attenuate the nociception resulting from direct stimulation of an ascending pain pathway as well as potentiating the analgesic effect of morphine on the stimulation of the pain pathway. We have previously used classical psychophysical procedures to determine the threshold for escape from the aversive stimulation of the mesencephalic reticular formation (MRF) in the study of nociception and analgesia in the rat (Wheeling et al., 1981; Unterwald et al., 1987; Izenwasser and Kornetsky, 1989; Sasson and Kornetsky, 1983; Sasson et al., 1986; Hubner and Kornetsky, 1972; Crosby et al., 2005). The advantage of the technique over the commonly used reflexive techniques is that an actual threshold can be determined and defined in terms of intensity of stimulation, e.g., μAmps, as opposed to reflexive techniques, i.e., the " tail-flick. "
    [Show abstract] [Hide abstract] ABSTRACT: The purpose of this experiment was to test in the rat the hypotheses that activation of the brain reward system would attenuate the effects of intracranial nociceptive stimulation and would potentiate the antinociceptive effects of morphine. In this experiment pain (nociception) was generated by electrical stimulation of a brain pain pathway, the mesencephalic reticular formation (MRF) of the rat. Reward pathway stimulation was to the medial forebrain bundle at the level of the lateral hypothalamus (MFB-LH). Current thresholds for escape from MRF stimulation were determined using a modification of the psychophysical methods of limits. MRF stimulation was delivered concurrently with different intensities of non-contingent MFB-LH stimulation. The effects of morphine and saline were determined under all stimulation conditions. Contrary to expectation MFB-LH stimulation significantly lowered MRF stimulation escape thresholds. Morphine administration elevated MRF thresholds in the absence of MFB-LH stimulation. However, this effect was blocked by concurrent MFB-LH stimulation. These findings, which mimic the effects of the opiate antagonist naloxone, i.e., potentiating of pain and antagonism of morphine's analgesic effects, suggest the presence of an endogenous opiate receptor antagonist.
    Full-text · Article · Feb 2010
    • "Morphine analgesia did not differ between young and aged rats using tail-flick latencies, but older animals showed a decreased analgesic response using a method measuring tailflick thresholds as well as escape thresholds from electrical stimulation of the mesencephalic reticular formation [249]. "
    [Show abstract] [Hide abstract] ABSTRACT: This paper is the 29th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning 30 years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17).
    Full-text · Article · Jan 2008
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