Antinociceptive effect of intrathecal administration of hypotaurine in rat models of inflammatory and neuropathic pain

Abstract

Hypotaurine is an intermediate in taurine biosynthesis from cysteine in astrocytes. Although hypotaurine functions as an antioxidant and organic osmolyte, its physiological role in the central nervous system remains unclear. This study used behavioral assessments to determine whether hypotaurine influenced nociceptive transmission in acute, inflammatory, and neuropathic pain. The tail flick, paw pressure, and formalin tests were performed in male Sprague-Dawley rats to examine the effects of the intrathecal administration of hypotaurine (100, 200, 400, 600 μg) on thermal, mechanical, and chemical nociception. Chronic constriction injury (CCI) to the sciatic nerve was induced in the rats, and the electronic von Frey test and plantar test were performed to assess the effects on neuropathic pain. To determine which neurotransmitter pathway(s) was involved in the action of hypotaurine, in this study, we examined how the antagonists of spinal pain processing receptors altered the effect of 600 μg hypotaurine. To explore whether hypotaurine affected motor performance, the Rotarod test was conducted. Hypotaurine had antinociceptive effects on thermal, mechanical, and chemical nociception in the spinal cord. In CCI rats, hypotaurine alleviated mechanical allodynia and thermal hyperalgesia. These effects were reversed completely by pretreatment with an intrathecal injection of strychnine, a glycine receptor antagonist. Conversely, hypotaurine did not affect motor performance. This study demonstrated that intrathecal hypotaurine suppressed acute, inflammatory, and neuropathic pain. Hypotaurine may regulate nociceptive transmission physiologically by activating glycinergic neurons in the spinal cord, and it is a promising candidate for treating various pain states.

Cysteine sulfinic acid decarboxylase activity of Aedes aegypti aspartate 1-decarboxylase: The structural basis of its substrate selectivity

“…Studies have indicated that hypotaurine was an antioxidant and a neurotransmitter influencing nociceptive transmission in vivo (Aruoma et al, 1988;Hara et al, 2011;Suzuki et al, 2007). Moreover, hypotaurine is a key intermediate in the taurine biosynthesis (Jerkins and Steele, 1992;Li et al, 2006;Ueki and Stipanuk, 2007).…”

Sex-specific hippocampal metabolic signatures at the onset of systemic inflammation with lipopolysaccharide in the APPswe/PS1dE9 mouse model of Alzheimer’s disease

“…5′-Methylthioadenosine, is indeed now seen as a key regulator of immune responses to inflammation and systemic infections (Albers, 2009, Wang et al, 2017), proven to mediate protection against LPS-induced inflammation in vitro (Hevia et al, 2004), but also to inhibit inflammation and reduce brain damage in animal models of neuroinflammation (Moreno et al, 2006). Furthermore, hypotaurine which has well established antioxidant properties (Fontana et al, 2004), was also found to effectively suppress inflammatory and neuropathic pain (Hara et al, 2012). Taurine and hypotaurine are present in elevated levels in the brain of the long-lived Snell Dwarf mouse (Vitvitsky et al, 2013), which exhibits reduced oxidative damage to the brain (Brown-Borg, 2006) and hypothalamic inflammation (Sadagurski et al, 2015).…”

Taurine as an Essential Neuromodulator during Perinatal Cortical Development

“…In accordance with this actions, animal studies reported anticonvulsive actions of taurine ( El Idrissi et al, 2003 ; El Idrissi and L’Amoreaux, 2008 ), which, however, were not completely replicated in humans (reviewed in Oja and Saransaari, 2013 ). In line with an inhibitory action in the spinal cord, taurine also has as a considerably antinociceptive effect ( Pellicer et al, 2007 ; Terada et al, 2011 ; Hara et al, 2012 ). In addition, taurine improves different in vitro correlates of memory formation ( Chepkova et al, 2002 ; del Olmo et al, 2003 ; Sergeeva et al, 2003 ) and accordingly augments learning and memory ( El Idrissi, 2008a ; Neuwirth et al, 2013 ).…”