Distribution of extracellular signal‐regulated kinase 1‐ and 2‐activated neurons in the rat periaqueductal gray matter after noxious stimulation

Abstract

The periaqueductal gray matter (PAG), the midbrain region made up of neuronal columns encircling the cerebral aqueduct, plays a key role in nociception. As the extracellular signal-regulated kinases (ERKs) 1 and 2 are activated after noxious stimulation, we analyzed the distribution of ERKactivated neurons in the PAG after visceral noxious stimulation. Ether-and urethane-anesthetized rats received an intraperitoneal injection of acetic acid or were left untreated and were perfused after 2 hr. Serial sections immunoreacted with an antibody selective for the activated ERKs. Significant ERK activation occurred only in the ether-anesthetized noxious stimulated rats. In these rats, we evaluated the number of ERK-activated neurons and their density as the ratio of the number of immunolabeled neurons to the extension of the region where they were located. ERK-activated neurons were more numerous in the lateral (LPAG) and ventrolateral (VLPAG) columns, but without significant differences. No ERK activation was seen in neurons of the most rostral PAG. The ERK-activated neurons were significantly denser at the intermediate level of the PAG. At the caudal level, they were denser in the LPAG and VLPAG columns, and in the DPAG column at the intermediate and rostral level. These findings suggest that noxious stimulation activates ERKs in neurons involved in the different functional activities related to nociception, overlapping in the PAG columns, and strengthens the role of PAG in integration. © 2005 Wiley-Liss, Inc.Key words: periaqueductal gray matter; nociception; extracellular signal-regulated kinases 1 and 2; immunohistochemistry; ratThe periaqueductal gray matter (PAG) is the midbrain region made up of neurons surrounding the cerebral aqueduct. It is involved in various important functional activities such as fear, anxiety, defensive reactions, and autonomic regulation. Its key role, however, is in pain processing (Bandler and Shipley, 1994; Behbehani, 1995;Westlund, 2000). The PAG is involved in the transmission and modulation of pain, acting on nociceptive ascending and descending systems through complex neural intrinsic circuits (Behbehani, 1995).Anatomical and functional data suggest that the PAG is made up of columns of neurons with different location from the aqueduct, extending for different distances along the cerebral aqueduct axis (Bandler and Shipley, 1994 dorsal (DPAG) column is involved in fear and anxiety processing (Behbehani, 1995), and the lateral (LPAG) and ventrolateral (VLPAG) columns play specific roles in coordinating different strategies for coping with distinct patterns of stress, threat, and noxious stimuli (Bandler and Shipley, 1994).Within the central nervous system, many extracellular stimuli, including noxious stimulation, are converted into specific cellular responses, activating signal-transduction systems such as the mitogen-activated protein kinase (MAPK) cascade, which in turn coordinates cellular activities such as gene transcription, protein synthesis, cell cycle machinery, ...

Extracellular signal‐regulated kinase activation in the chronic constriction injury model of neuropathic pain in anaesthetized rats

“…Consistently, few studies have detected ERK1/2 activation in PAG. Exemplifying, discrete increases in pERK1/2 neuronal density were found in ether‐anaesthetized noxious‐stimulated rats (Gioia et al., ). Also in LPB and EW, no changes in the ERK1/2 activation pattern were observed in CCI or after acute noxious stimulation, despite their roles in pain modulation (Basbaum and Fields, ; Gauriau and Bernard, ).…”

Loss of dopamine D1 receptors and diminished D1/5 receptor-mediated ERK phosphorylation in the periaqueductal gray after spinal cord lesion

“…Since coupling of ERK and CREB phosphorylation to D1 receptor activation has been well established in other brain regions (Brami-Cherrier et al, 2002; Acquas 2007; Papadeas et al, 2008; Pascoli et al, 2012), and as ERK1,2 is phosphorylated in the PAG in response to diverse stimuli (Gioia et al, 2005, Macey et al, 2009; Nasser and McNally, 2013; Sanna et al, 2014; Macey et al, 2015), we selected pERK1,2 and pCREB as markers to assess D1 receptor-mediated signal transduction. As a first step toward addressing this point, we used an in vivo approach to investigate the effect of administration of SKF 81297, a D1/5 receptor agonist, on ERK1,2 and CREB phosphorylation in the PAG of naïve mice.…”

Identification of cholinergic and non-cholinergic neurons in the pons expressing phosphorylated cyclic adenosine monophosphate response element-binding protein as a function of rapid eye movement sleep

“…Unlike the observation of Verret and colleagues (2005), in the present study we did not observe any changes in pCREB activation as a function of REM sleep in the PAG. This is not a surprising difference because it is a well-known fact that PAG neurons are activated in response to stress-induced pain (Dostrovsky et al, 1983; Auerbach et al, 1984; Fardin et al, 1984; Bandler and Shipley, 1994; Giola et al, 2005). Thus, this difference further supports our suggestion that the use of flowerpot method for this type of study is problematic and is not appropriate.…”