Alteration of Descending Modulation of Nociception during the Course of Monoarthritis in the Rat

Abstract

Diffuse noxious inhibitory controls (DNIC), which involve supraspinal structures and modulate the transmission of nociceptive signals, were investigated at different stages during the development of adjuvant-induced monoarthritis in the rat. After behavioral evaluation, recordings of trigeminal convergent neurons were performed in anesthetized animals with acute (24-48 hr) or chronic (3-4 weeks) monoarthritis of the ankle. Inhibitions of C-fiber-evoked neuronal responses during and after the application of noxious conditioning stimuli to the ankle were measured to evaluate DNIC. The conditioning stimuli consisted of mechanical (maximal flexion and graded pressures) and graded thermal stimuli and were applied alternately to normal and arthritic ankles. Behaviorally, the two groups of animals exhibited a similar increased sensitivity to mechanical stimuli applied to the arthritic joint (i.e., an increased ankle-bend score and a decreased vocalization threshold to pressure stimuli). However, they showed different electrophysiological profiles. In the animals with acute monoarthritis, the DNIC-induced inhibitions produced by mechanical or thermal stimulation of the arthritic joint were significantly increased at all intensities compared with the normal joint. In contrast, in the chronic stage of monoarthritis, the DNIC-induced inhibitions triggered by thermal or pressure stimuli were similar for both ankles, except with the most intense mechanical stimuli. This discrepancy between the behavioral and electrophysiological findings suggests that inputs activated during chronic monoarthritis may fail to recruit DNIC and may thus be functionally different from those activated in the acute stage of inflammation.

Blockade of Opioid Receptors in the Medullary Reticularis Nucleus Dorsalis, but not the Rostral Ventromedial Medulla, Prevents Analgesia Produced by Diffuse Noxious Inhibitory Control in Rats With Muscle Inflammation

“…54 In agreement, in animals with inflammation, DNIC analgesia was greater in the acute stage at a time when there is enhanced inhibition, but not in a more chronic stage. 17,18 Thus, these data support the conclusion that there is a shift in the balance between uninjured and injured animals that depends on the time after injury.…”

“…These data agree with prior animal studies showing that DNIC is more effective in animals with hind paw inflammation or neuropathic pain when recording central nociceptive neurons in the dorsal horn or trigeminal nucleus. 17,18 Interestingly, in humans, cold-pressor-induced DNIC responses applied concomitantly with a hypertonic saline-induced muscle pain resulted in less analgesia. 1 This may be comparable to that observed in the current study when the DNIC-conditioning stimulus was given with the muscle withdrawal threshold stimulus which resulted in no analgesia in animals without tissue injury.…”

Non‐linear morphine‐induced depression of spinal excitation following long‐term potentiation of C fibre‐evoked spinal field potentials

“…According to the above, this may be due to deactivation of descending inhibition, which can occur within seconds after cessation of the triggering noxious stimulus (Danziger et al, 1999(Danziger et al, , 2001 or within several minutes following application of strong stimuli (Le Bars, 2002), and a consequent loss of synergistic effect of MOR, inasmuch as administration of higher MOR concentrations rapidly resulted in a depression of evoked field potentials to near basal levels. According to the above, this may be due to deactivation of descending inhibition, which can occur within seconds after cessation of the triggering noxious stimulus (Danziger et al, 1999(Danziger et al, , 2001 or within several minutes following application of strong stimuli (Le Bars, 2002), and a consequent loss of synergistic effect of MOR, inasmuch as administration of higher MOR concentrations rapidly resulted in a depression of evoked field potentials to near basal levels.…”

Plasticity in Excitatory Amino Acid Receptor-Mediated Descending Pain Modulation after Inflammation

“…Both inhibitory and facilitatory descending influences on nociceptive transmission can be simultaneously engaged throughout the RVM, a structure that includes the midline nucleus raphe magnus (NRM) and adjacent lateral reticular formation (Fields et al, 1983;Aimone and Gebhart, 1986). Although most earlier studies focused on responses to transient noxious stimuli (Fields and Basbaum, 1978;Fields et al, 1983;Sandkü hler and Gebhart, 1984;Willis, 1988), recent evidence suggests that descending pathways from RVM also modulate spinal nociceptive transmission during inflammatory pain, and play a role in the development of persistent pain Montagne and Oliveras, 1994;Ren and Dubner, 1996;Wei et al, 1998;Danziger et al, 1999;Terayama et al, 2000a). A number of reports demonstrates that descending pain modulation is not fixed but exhibits changes in response to persistent noxious input under various conditions Ren and Dubner, 1996;Danziger et al, 1999;Dubner and Ren, 1999;Hurley and Hammond, 2000).…”

“…Although most earlier studies focused on responses to transient noxious stimuli (Fields and Basbaum, 1978;Fields et al, 1983;Sandkü hler and Gebhart, 1984;Willis, 1988), recent evidence suggests that descending pathways from RVM also modulate spinal nociceptive transmission during inflammatory pain, and play a role in the development of persistent pain Montagne and Oliveras, 1994;Ren and Dubner, 1996;Wei et al, 1998;Danziger et al, 1999;Terayama et al, 2000a). A number of reports demonstrates that descending pain modulation is not fixed but exhibits changes in response to persistent noxious input under various conditions Ren and Dubner, 1996;Danziger et al, 1999;Dubner and Ren, 1999;Hurley and Hammond, 2000). The activity of the RVM pain modulatory circuitry increases during persistent inflammation and gives rise to enhanced descending pain inhibition Ren and Dubner, 1996;Wei et al, 1998;Hurley and Hammond, 2000;Terayama et al, 2000a) as well as facilitation Wei et al, 1999;Terayama et al, 2000a).…”