chloramine-t and Pain

The well-known active chlorine compound chloramine T (CAT) with broad-spectrum antimicrobial activity is in common therapeutic use for leg ulcers with purulent coatings; however, this treatment is painful. The tolerability of the less aggressive N-chlorotaurine (NCT), an endogenous compound also produced in vivo by stimulated human granulocytes, could be superior.. To assess the tolerability and efficacy of NCT in the cleaning of purulent coatings in chronic leg ulcers in comparison with CAT.. In a double-blind, randomized phase IIb clinical study 40 patients were treated for a median of 7 days (range 3-14) with a 1% aqueous solution of either NCT (20 subjects) or CAT (20 subjects) by twice-daily application of dressings soaked in the test solutions. Criteria for evaluation of tolerability were intensity and duration of pain caused by the ulcer therapy and scores of tissue toxicity (necrosis, granulation tissue and re-epithelialization). Therapeutic efficacy was graded as scores of intensity of purulent coating of the ulcers.. The concentration tolerated in vitro by human epidermoid carcinoma cells was at least 10-fold higher for NCT (0.01%) compared with CAT (0.0001-0.001%). There was significantly less pain caused by NCT compared with CAT (P < 0.05) on days 1 and 4 and a trend for a shorter duration of pain (P = 0.093). The scores of intensity of coating improved without difference in both treatment groups, whereas granulation and re-epithelialization appeared earlier in the NCT group (P < 0.05). Non-quantitative microbiological cultures from ulcer smears revealed persistence of colonization by bacterial species in approximately half of both treatment groups.. Both active chlorine compounds were helpful in reducing purulent coatings. Because of its lower toxicity and better tolerability, NCT is of advantage in the treatment of leg ulcers.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Anti-Infective Agents, Local; Chloramines; Chronic Disease; Dermatologic Agents; Double-Blind Method; Drug Evaluation; Female; Humans; Leg Ulcer; Male; Middle Aged; Pain; Taurine; Tosyl Compounds; Treatment Outcome; Wound Healing

Voltage-gated Na(+) channels regulate neuronal excitability by generating the upstroke of action potentials. The α-subunits Nav1.7 and Nav1.8 are required for normal function of sensory neurons and thus for peripheral pain processing, but also for an increased excitability leading to an increased pain sensitivity under several conditions associated with oxidative stress. While little is known about the direct effects of oxidants on Nav1.7 and Nav1.8, a recent study on mouse dorsal root ganglion neurons suggested that oxidant-induced alterations of nociceptor excitability are primarily driven by Nav1.8. Here we performed whole-cell patch clamp recordings to explore how oxidation modulates functional properties of recombinant Nav1.7 and Nav1.8 channels. The strong oxidant chloramine-T (ChT) at 100 and 500µM induced a shift of the voltage-dependency of activation towards more hyperpolarized potentials. While fast inactivation was stabilized by 100µM ChT, it was partially removed by 500µM ChT on both α-subunits (Nav1.7

Topics: Action Potentials; Chloramines; Ganglia, Spinal; HEK293 Cells; Humans; Ion Channel Gating; Membrane Potentials; NAV1.7 Voltage-Gated Sodium Channel; NAV1.8 Voltage-Gated Sodium Channel; Oxidation-Reduction; Pain; Patch-Clamp Techniques; Sodium; Sodium Channels; Tetrodotoxin; Tosyl Compounds

Redox modulation of fast inactivation has been described in certain cloned A-type voltage-gated K(+) (Kv) channels in expressing systems, but the effects remain to be demonstrated in native neurons. In this study, we examined the effects of cysteine-specific redox agents on the A-type K(+) currents in acutely dissociated small diameter dorsal root ganglion (DRG) neurons from rats. The fast inactivation of most A-type currents was markedly removed or slowed by the oxidizing agents 2,2'-dithio-bis(5-nitropyridine) (DTBNP) and chloramine-T. Dithiothreitol, a reducing agent for the disulfide bond, restored the inactivation. These results demonstrated that native A-type K(+) channels, probably Kv1.4, could switch the roles between inactivating and non-inactivating K(+) channels via redox regulation in pain-sensing DRG neurons. The A-type channels may play a role in adjusting pain sensitivity in response to peripheral redox conditions.

Topics: Animals; Chloramines; Cysteine; Dithiothreitol; Ganglia, Spinal; Kv Channel-Interacting Proteins; Kv1.4 Potassium Channel; Neurons, Afferent; Oxidants; Oxidation-Reduction; Pain; Pyridines; Rats; Rats, Wistar; Tosyl Compounds