Activity-induced plasticity in brain stem pain modulatory circuitry after inflammation

Abstract

Brain stem descending pathways modulate spinal nociceptive transmission. In a lightly anesthetized rat preparation, we present evidence that such descending modulation undergoes time-dependent changes following persistent hindpaw inflammation. There was an initial decrease and a subsequent increase in the excitability of neurons in the rostral ventromedial medulla (RVM) involving facilitation and inhibition. These changes were most robust after stimulation of the inflamed paw although similar findings were seen on the non-inflamed paw and tail. The enhanced descending modulation appeared to be mediated by changes in the activation of the NMDA excitatory amino acid receptor. These findings demonstrate the dynamic plasticity of the pain modulating pathways in response to persistent tissue injury.

Inflammation-Induced Enhancement of the Visceromotor Reflex to Urinary Bladder Distention: Modulation by Endogenous Opioids and the Effects of Early-in-Life Experience With Bladder Inflammation

“…Similar views have been advanced to account for the loss of spinal morphine suppression of somatic nociception and tactile allodynia following tight ligation of L5/L6 nerves. 24 There also is abundant evidence that descending inhibitory systems derived from either the rostroventral medulla (RVM) 11,32 or the locus coeruleus (LC) [33][34][35][36] are recruited following inflammation of somatic tissue. While these descending systems are present at birth, they are only partially functional by P10-P12 and become functionally mature by P21.…”

“…26 This enhanced bladder response was paralleled by a more global bladder hypersensitivity, manifested as increased micturition frequency 26 and decreased thresholds for micturition reflexes during cystometry. 8 Other studies of primary hyperalgesia and inflammation involving either the knee joint 31 or the hindpaw 28,39 have shown that descending inhibitory systems are progressively engaged during the first 24 hrs of acute inflammation and act to suppress somatic hyperalgesia (see also 11,27,[32][33][34][35][36] ). These data suggested the possibility that the urinary bladder hypersensitivity produced by acute bladder inflammation in the adult rat may be concomitantly suppressed by inflammation-induced activation of an inhibitory system 37,38 and that the enhancement effect we observed with neonatal exposure to zymosan might be due to impairment of this inhibitory system.…”

Targeting the NMDA Receptor Subunit NR2B for the Treatment of Neuropathic Pain

“…Microinjection of selective NMDA receptor antagonists prevented the inflammation-induced increase in RVM excitability. 68 Thus, the enhanced descending modulation appears to be mediated by changes in the activation of the NMDA receptor in the RVM.…”

Morphine preferentially activates the periaqueductal gray–rostral ventromedial medullary pathway in the male rat: A potential mechanism for sex differences in antinociception

“…One possibility is that in females, morphine activates a pain facilitation network. A PAG-RVM pain facilitatory system has been shown to contribute to hyperalgesia produced by opiate withdrawal (Bederson et al, 1990), chronic inflammation (Terayama et al, 2000,Guan et al, 2002, and morphine tolerance ). Interestingly, morphine-induced hyperalgesia is significantly more pronounced in females in comparison to males (Holtman and Wala, 2005).…”