Morphine or U‐50,488 suppresses fos protein‐like immunoreactivity in the spinal cord and nucleus tractus solitarii evoked by a noxious visceral stimulus in the rat

Abstract

Immunohistochemical visualization of Fos protein, the nuclear phosphoprotein product of the early-immediate gene c-fos, permits identification of populations of neurons that are activated in response to a variety of stimuli. This study examined the distribution of Fos-like immunoreactive (FLI) neurons in the spinal cord and the nucleus tractus solitarii (NTS) of the caudal medulla evoked by a noxious visceral stimulus in the unanesthetized rat. It also compared the inhibition of pain behavior and Fos expression by a mu-selective opioid agonist, morphine, and a kappa-selective opioid agonist, U-50,488. Intraperitoneal injection of 3.5% acetic acid in the unanesthetized rat evoked the expression of FLI in a discrete population of spinal cord neurons, the distribution of which closely mirrored the spinal terminations of visceral primary afferents. Specifically, FLI neurons were concentrated in laminae I, IIo, V, VII, and X. Large numbers of Fos-immunoreactive neurons were also present in the NTS of the caudal medulla, most likely as a result of spinosolitary tract and vaginal afferent input. The number of labeled neurons in both the spinal cord and the NTS was significantly correlated with the number of abdominal stretches, a pain behavior measure. Both morphine (1-10 mg/kg s.c.) and U-50,488 (3-30 mg/kg s.c.) produced a dose-dependent inhibition of the pain behavior in these animals and a dose-dependent suppression of the number of FLI neurons in both the spinal cord and in the NTS; complete suppression of FLI neurons was, however, not necessary for the production of antinociception. Furthermore, although equianalgesic doses of morphine and U-50,488 reduced the number of labelled neurons in the spinal cord to a comparable extent, morphine reduced the number of immunoreactive neurons in the NTS to a greater extent than did U-50,488. These results suggest that morphine and U-50,488 have comparable effects on the transmission of visceral nociceptive messages by spinal neurons, but differentially affect the autonomic response to noxious visceral stimuli.

Nociception after intraperitoneal injection of a sodium pentobarbitone formulation with and without lidocaine in rats quantified by expression of neuronal c-fos in the spinal cord – a preliminary study

“…The presence of the FLI neurones in laminae I, II, V and X of the spinal dorsal horn is in agreement with the fact that these laminae mainly receive input from visceral nociceptive fibres (Mené trey et al 1989, Hammond et al 1992, Clement et al 2000. The FLI neurones were found in the entire length of the spinal cord examined which is in accordance with findings described in the above-referred papers and in accordance with a global intraperitoneal distribution of the injected fluid.…”

“…Mené trey et al (1989), Hammond et al (1992) and Clement et al (2000) applied in their studies a dose volume of 0.5 mL/rat. In the behavioural study of Ambrose et al (2000), a dose volume of 1.5 mL/kg was applied in order to obtain a lethal effect.…”

“…Thus, the positive effect of the addition of lidocaine has been shown at a neuronal and behavioural level. In a study with intraperitoneal injection of a formulation of acetic acid in rats, Hammond et al (1992) showed that spinal c-fos expression and pain behaviour were reduced in animals pretreated with morphine as an analgesic agent. The pain behaviour was significantly reduced when the number of c-fos-expressing neurones was reduced to 50%, and the pain behaviour was almost eliminated when c-fos expression was further reduced to 35%.…”

Tooth Movement Activates the Central Amygdala and the Lateral Hypothalamus by the Magnitude of the Force Applied

“…18,19 The dosedependent effects of morphine on the number of Fos-IR cells in the superficial layers of the ipsilateral trigeminal subnucleus caudalis was observed after experimental tooth movement. 3 A reduction of Fos-IR cells in the parabrachial nucleus by morphine treatment, which was reversible by pretreatment with naloxone, was seen after tooth movement.…”

c-Fos expression in the spinal cord and pain-related symptoms induced by chronic arthritis in the rat are prevented by pretreatment with Freund adjuvant

“…This work has led to numerous studies related to pain research. After several years of investigations, there is accumulating evidence that various nociceptive peripheral stimuli result in c-j& expression at the spinal cord level (Hunt et al, 1987;Bullitt, 1989Bullitt, , 1990Bullitt, , 1991Draisci and Iadarola, 1989;Menetrey et al, 1989;Williams et al, 1989;Presley et al, 1990;Tolle et al, 1990;Wisden et al, 1990;Gogas et al, 199 1;Herdegen et al, 199 1;Naranjo et al, 199 1;Abbadie and Besson, 1992a,b;Bullitt et al, 1992;Hammond et al, 1992;Hylden et al, 1992;Leah et al, 1992;Lee and Beitz, 1992;Noguchi et al, 1992;Abbadie and Besson, 1993). Taking into account the numerous investigations based on c-Fos experiments, it is reasonable to assume that dorsal horn neurons receiving noxious inputs (see references in Besson and Chaouch, 1987) preferentially express C-$X when activated by noxious stimulation.…”