The behavioral importance of dynamically activated descending inhibition from the nucleus reticularis gigantocellularis pars alpha. (University Hospital of Wales, Cardiff, United Kingdom) Pain 2001;92:53–62.

Abstract

This study demonstrates the effects of nucleus reticularis gigantocellularis pars alpha (GiA) on the behavioral response during application of standardized noxious stimuli. As this system is activated in response to noxious stimulation, it is possible that chronic pain states may also activate GiA. Therefore, this study investigated this possibility in animals following partial sciatic nerve ligation (an animal model of chronic pain). Male Wistar rats (280–310 g) were anesthetized with halothane (0.5% to 2% in O2). Guide cannulae for microinjections were stereotaxically placed above GiA. In one group of animals the sciatic nerve was partially litigated. Animals were allowed to recover for 4–6 days. The responses of each animal during the formalin test and the tail flick test were recorded on different days. Microinjections (0.5 μl) of either γ‐aminobutyric acid (GABA, 200 mM), D‐L homocysteic acid (DLH, 25 mM), or 0.9% saline (as control) into GiA were preformed during these tests in a randomized, blind manner. In animals without sciatic nerve ligation, microinjection of GABA to GiA did not significantly affect the animal's response during the tail flick test. However, microinjection of DLH significantly increased the latency of tail flick from 6.2 ± 0.8 to 8.4 ± 0.5 seconds for up to 15 minutes. Microinjection of GABA to GiA increased the behavioral response to formalin between 10 and 20 minutes postinjection, while microinjection of DLH reduced this response at all time points except 10 minutes postinjection (n = 8, p < 0.05, Mann‐Whitney U‐test). In animals with sciatic nerve ligation, microinjections (0.5 μl) of either GABA (200 mM), or saline (as control) into GiA contralateral to the partial sciatic ligation were performed during these tests in a randomized, blind manner. Partial sciatic ligation significantly reduced the behavioral response to contralaterally applied formalin from 15 minutes postinjection onwards, compared to controls without sciatic nerve ligation. Microinjection of GABA GiA significantly increased the behavioral response to formalin from 20 to 50 minutes postinjection. The inactivation of GiA only causes behavioral effects in nociceptive tests of a long enough duration to activate the system (ie, the formalin test but not the tail flick test). Chemical activation of the system affects both tests. Conclude that these data strongly support the concept of an important analgesic system that is activated in response to noxious stimulation, and subsequently acts to reduce behavioral responses to noxious stimuli.Comment by Leland Lou, M.D. This is a rat study that looked at the presence of inhibitory spinal multireceptive cells modifying and decreasing the behavioural response to noxious stimuli. While no direction was given as to the source of noxious stimuli inhibition in chronic pain, great effort was made to report a possible differential response of the C‐fiber pain system versus the large sensory fibers. After review it seems that the authors believed that the nucleus reticularis gigantocellularis pars alpha maybe a central processor of the inhibitory response. It is still too early to assess the clinical impact of this study.