Induction by carrageenan inflammation of prepronociceptin mRNA in VR1-immunoreactive neurons in rat dorsal root ganglia
Introduction
Nociceptin, also known as orphanin FQ, is peptide which was discovered as an endogenous ligand for opioid receptor-like 1 (ORL1) receptor (Meunier et al., 1995, Reinscheid et al., 1995). In these reports, an intracerebroventricular injection of nociceptin was shown to induce hyperalgesia by hot plate and tail-flick tests in mice (Meunier et al., 1995, Reinscheid et al., 1995). Thereafter, some reports showed that an intrathecal injection of nociceptin induced both thermal hyperalgesia and mechanical allodynia (Hara et al., 1997, Sakurada et al., 1999, Minami et al., 2000). On the contrary, other reports showed that an intrathecal injection of nociceptin induced thermal analgesia (King et al., 1997, Tian et al., 1997). Thus, although the precise role of nociceptin is unknown, this peptide may be involved in the regulation of nociceptive information in the spinal dorsal horn.
When examined with reverse transcription-polymerase chain reaction (RT-PCR), the highest level of prepronociceptin (PPN) mRNA expression is localized in the cerebral cortex, pons/medulla, and midbrain in rats; a moderate level in the cerebellum, hypothalamus, and striatum; a low level in the thalamus, hypothalamus, and spinal cord (Andoh et al., 1997). Although there is little or no expression of PPN mRNA in the dorsal root ganglia (DRG) of the naive rats, a peripheral inflammation caused by carrageenan was found to produce a rapid induction of PPN mRNA there (Andoh et al., 1997). The induction peaked 30 min after carrageenan injection; it followed peripheral inflammation and preceded thermal hyperalgesia, suggesting that nociceptin induced in primary sensory neurons by peripheral inflammation is involved in thermal hyperalgesia. The findings generate interest in the type of primary sensory neurons expressing PPN mRNA after peripheral inflammation.
Vanilloid receptor subtype 1 (VR1) was cloned as a capsaicin receptor (Caterina et al., 1997). VR1 receptor is activated by capsaicin, noxious heat, extracellular acidification, anandamide and lipoxygenase products and induces the influx of cations, particularly Na+ and Ca2+ ions (Caterina et al., 1997, Tominaga et al., 1998, Zygmunt et al., 1999, Hwang et al., 2000). A high level of VR1 mRNA is expressed in the DRG and trigeminal ganglia (Caterina et al., 1997). Little or no level of VR1 mRNA is expressed in the brain and spinal cord (Caterina et al., 1997, Tominaga et al., 1998), although RT-PCR reveals the expression in some brain regions (Sasamura et al., 1998, Sasamura and Kuraishi, 1999). VR1-expressing primary sensory neurons are associated with nociceptive transmission. Therefore, in the present study, we investigated the localization of PPN mRNA in primary sensory neurons of rats after peripheral inflammation and co-expression of PPN mRNA and VR1 receptors in the sensory neurons.
Section snippets
Animals
Male Sprague–Dawley rats (Japan SLC Ltd., Shizuoka) were used at 5 weeks old. The animals were kept under controlled temperature (22±1°C), humidity (55±10%), and light (lights on 07:00–19:00 h). Food and water were freely available.
Materials
The materials were obtained from the following sources; alkaline phosphate-conjugated anti-digoxigenin (DIG) antibody, 5-bromo-4-chloro-4-indonyl-phosphate 4-toluidine salt, 4-nitroblue tetrazolium chloride, and proteinase K were from Boehringer Mannheim
Carrageenan-induced expression of PPN mRNA
There were no cells positive for PPN mRNA in the DRG of untreated rat (Fig. 1A). Half an hour after carrageenan injection, there were many neurons strongly positive for PPN mRNA in the DRG on the treated side (Fig. 1B). Positive neurons were also observed at 1 and 3 h after carrageenan injection, but signal intensity and the number of positive cells were less than those at 0.5 h (Fig. 1C and D). The positive neurons were small or medium in diameter (<30 μm) (Fig. 1B–D). The percentage of PPN
Discussion
Although there were no cells positive for PPN mRNA in the DRGs of normal rats, an injection of carrageenan into the hind paw produced the induction of PPN mRNA in DRG neurons. The induction was rapid in onset and short-lasting, and the time course of the induction was similar to the detection using RT-PCR (Andoh et al., 1997), in which the induction level peaked 30 min after carrageenan, then decreased rapidly, and returned to normal by 6 h.
The sensory neurons that expressed PPN mRNA after
References (25)
- et al.
Unaltered peripheral excitatory actions of nociceptin contrast with enhanced spinal inhibitory effects after carrageenan inflammation: an electrophysiological study in the rat
Pain
(2000) - et al.
Anti-hyperalgesic and anti-allodynic effects of intrathecal nociceptin/orphanin FQ in rats after spinal cord injury, peripheral nerve injury and inflammation
Pain
(1998) - et al.
Spinal analgesic activity of orphanin FQ/nociceptin and its fragments
Neurosci. Lett.
(1997) - et al.
Characterization of nociceptin/orphanin FQ-induced pain responses in conscious mice: neonatal capsaicin treatment and N-methyl-d-aspartate receptor GluRε subunit knockout mice
Neuroscience
(2000) - et al.
Involvement of tachykinin NK1 receptors in nociceptin-induced hyperalgesia in mice
Brain Res.
(1999) - et al.
Peripheral and central actions of capsaicin and VR1 receptor
Jpn. J. Pharmacol.
(1999) - et al.
Vanilloid (capsaicin) receptors in the rat: distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment
Brain Res.
(1995) - et al.
The cloned capsaicin receptor integrates multiple pain-producing stimuli
Neuron
(1998) - et al.
Effects of intrathecal orphanin FQ on a flexor reflex in the rat after inflammation or peripheral nerve section
Eur. J. Pharmacol.
(1999) - et al.
Effects of intrathecally administered nociceptin, an opioid receptor-like1 (ORL1) receptor agonist, on the thermal hyperalgesia induced by carrageenan injection into the rat paw
Brain Res.
(1997)
Ethical guidelines for investigations of experimental pain in conscious animals. Pain
Nociceptin gene expression in rat dorsal root ganglia induced by peripheral inflammation
Neuroreport
Cited by (32)
Endogenous Nociceptin System Involvement in Stress Responses and Anxiety Behavior
2015, Vitamins and HormonesCitation Excerpt :Compelling evidence suggests that N/OFQ has significant potential in the regulation of inflammation, N/OFQ reduces inflammation-induced thermal hyperalgesia (Yamamoto et al., 1997; Hao, Xu, Wiesenfeld-Hallin, & Xu, 1998), exerts depression on spinal nociceptive input during peripheral inflammation (Xu, Grass, Wiesenfeld-Hallin, & Xu, 1999), inhibits antidromic vasodilatation (Häbler et al., 1999), and attenuates pronociceptive and proinflammatory tachykinins from peripheral sensory nerve endings (Giuliani & Maggi, 1996; Helyes, Németh, Pintér, & Szolcsányi, 1997; Németh et al., 1998) that could account for N/OFQ-induced antinociceptive and anti-inflammatory effects. Carrageenan-induced peripheral inflammation upregulates preproN/OFQ mRNA, N/OFQ peptide, and NOP binding in primary sensory neurones of dorsal root ganglia (Andoh, Itoh, & Kuraishi, 1997; Itoh et al., 2001), and dorsal horn (Fu, Wang, Wang, Yu, & Wu, 2007; Fu, Zhu, Wang, & Wu, 2007) in addition to the hypothalamus (Rosén, Lundeberg, Bytner, & Nylander, 2000) revealing plasticity in the N/OFQ system. Pain patients have elevated serum N/OFQ that is augmented in patients with long-lasting chronic pain (Ko, Kim, Woo, & Kim, 2002), although females with fibromyalgia syndrome have lower plasma N/OFQ (Anderberg, Liu, Berglund, & Nyberg, 1998) suggesting that a correlation between pain and serum N/OFQ may depend on factors such as the presence of inflammation, gonadal steroids, and stress.
Lipopolysaccharides and trophic factors regulate the LPS receptor complex in nodose and trigeminal neurons
2014, NeuroscienceCitation Excerpt :Thirdly, we examined whether activation of the LPS receptor leads to changes in N/OFQ expression in these neurons. We used this opioid peptide as a marker because it is expressed by trigeminal and nodose neurons (Jia et al., 2002; Hou et al., 2003) and it is associated with behavioral changes in models of neuropathic and inflammatory pain (Itoh et al., 2001; Chen et al., 2007). Postnatal day 5 (from now on P5) CD-1 mice were used in all experiments.
Involvement of temporomandibular joint P2X3 and P2X2/3 receptors in carrageenan-induced inflammatory hyperalgesia in rats
2010, European Journal of PharmacologyPeripheral anti-nociceptive effect of nociceptin/orphanin FQ in inflammation and stress-induced colonic hyperalgesia in rats
2009, PainCitation Excerpt :TRPV1 immunoreactivity, in the thoraco-lumbar and lumbo-sacral dorsal root ganglia neurons, is increased after TNBS-induced colitis in rat, confirming its role in the development of visceral hyperalgesia [24,37] . Moreover, in inflammation, pre-pro N/OFQ mRNA is co-expressed with TRPV1 receptors in primary afferent neurons [23], supporting the idea of a possible interaction between the two systems in the control of visceral pain, under inflammatory conditions. Indeed TRPV1 positive nerve fibers, co-expressing tachykinins (Substance P and neurokinins) and calcitonin gene-related peptide (CGRP), are present both in primary afferent neurons and intrinsic nerves of the gut [20].
Ovulation
2006, Knobil and Neill's Physiology of ReproductionThe Peripheral Sensory Nervous System: Dorsal Root Ganglion Neurons
2005, Peripheral Neuropathy: 2-Volume Set with Expert Consult Basic