Spinal Reflexes and Windup In Vitro: Effects of Analgesics and Anesthetics

Abstract

The spinal cord is the first relay center for nociceptive information. Following peripheral injury, the spinal cord sensitizes. A sign of spinal sensitization is the hyper-reflexia which develops shortly after injury and can be detected in the isolated spinal cord as a "memory of pain." In this context, it is easy to understand that many analgesic compounds target spinally located sites of action to attain analgesia. In vitro isolated spinal cord preparations have been used for a number of years, and experience on the effects of compounds of diverse pharmacological families on spinal function has accumulated. Recently, we have proposed that the detailed study of spinal segmental reflexes in vitro may produce data relevant to the evaluation of the analgesic potential of novel compounds. In this review, we describe the main features of segmental reflexes obtained in vitro and discuss the effects of compounds of diverse chemical nature and pharmacological properties on such reflexes. Our aim was to compare the different profiles of action of the compounds on segmental reflexes in order to extract clues that may be helpful for pharmacological characterization of novel analgesics.

Faradaic Pixels for Precise Hydrogen Peroxide Delivery to Control M‐Type Voltage‐Gated Potassium Channels

“…These channels are recognized as therapeutic targets for regulating neuronal excitability. [28,32] We suggest that peroxide-mediated enhancement of potassium M-currents can be a possible therapeutic approach to this end, and exploration of faradaic devices in excitable cell models and in vivo is a future goal. In this present work, using single-cell electrophysiology protocols, we found that the peroxide-delivery pixel devices unambiguously enhanced M-currents of peroxide-sensitive Kv7.2/7.3 ion channels.…”

“…[26,30] Neuropathic pain, commonly observed in cancer patients, is a further condition that is being associated with impaired Kv7.2/7.3 function and hyperexcitability. [31][32][33] According to more recent work by Gamper et al physiological concentrations of H 2 O 2 can activate Kv7.2/7.3 and enhance M-currents, making it a potentially potent therapeutic with a desired anti-excitable effect/silencing effect. [23] For this reason, we have chosen this type of ion channel as a target for faradaic H 2 O 2 -based stimulation in this work.…”

Neonatal Maternal Deprivation Enhances Presynaptic P2X7 Receptor Transmission in Insular Cortex in an Adult Rat Model of Visceral Hypersensitivity

“…IC also modulates pain through affecting middle cingulate cortex, periaqueductal gray, locus coeruleus, the nucleus accumbens, or raphe nucleus . The spinal cord, the first relay center for nociceptive processing, is worthy of exploring pain mechanism and effects of antinociceptive drugs . The detailed neural circuitry among these areas definitely needs to be further investigated.…”

Implication of Kv7 Channels in the Spinal Antinociceptive Actions of Celecoxib

“…Digital band-pass filtering of the original DC signal between 200 and 1200 kHz allowed us to generate an AC channel to collect fast spike-like events produced by the firing of action potentials in motor neurones (Rivera-Arconada et al, 2016). Events crossing an amplitude threshold were counted in a time window between 100 and 950 milliseconds from stimulus artifact and summated to obtain the total spike counts to each train of stimuli.…”