Mirror-Image Pain Update: Complex Interactions Between Central and Peripheral Mechanisms.

The appearance of contralateral effects after unilateral injury has been shown in various experimental pain models, as well as in clinics. They consist of a diversity of phenomena in contralateral peripheral nerves, sensory ganglia, or spinal cord: from structural changes and altered gene or protein expression to functional consequences such as the development of mirror-image pain (MP). Although MP is a well-documented phenomenon, the exact molecular mechanism underlying the induction and maintenance of mirror-like spread of pain is still an unresolved challenge.

Botulinum toxin type a antinociceptive activity in trigeminal regions involves central transcytosis.

Objective: Botulinum toxin type A (BoNT-A) provides lasting pain relief in patients with craniofacial pain conditions but the mechanisms of its antinociceptive activity remain unclear. Preclinical research revealed toxin axonal transport to the central afferent terminals, but it is unknown if its central effects involve transsynaptic traffic to the higher-order synapses. To answer this, we examined the contribution of central BoNT-A transcytosis to its action in experimental orofacial pain.

The safety of botulinum neurotoxin type A's intraarticular application in experimental animals.

In vivo studies of botulinum neurotoxin type A (BoNT-A) enabled characterization of its activity in the nociceptive sensory system separate from its preferred action in motor and autonomic nerve terminals. However, in the recent rodent studies of arthritic pain which employed high intra-articular (i.a.

What have we learned about antinociceptive effect of botulinum toxin type A from mirror-image pain models?

Mirror pain represents pain with complex pathophysiological background experienced at both sides of the body, usually after unilateral injury. Although observed almost 10 years ago, the phenomenon of bilateral antinociceptive effect of botulinum toxin type A (BoNT/A) following its unilateral administration in experimental mirror-image pain (MP) models remains challenging and intriguing task to explain. Data generated so far using MP models and mechanisms behind this unique feature of BoNT/A might influence the overall understanding of its mechanism of antinociceptive action.

Resolving Issues About Efficacy and Safety of Low-Dose Codeine in Combination Analgesic Drugs: A Systematic Review.

Introduction: The objective of this systematic review is to reflect on assumptions in relation to codeine use in combination with other analgesics.

Methods: MEDLINE was searched according to the predetermined keywords and criteria. Only English language studies were taken into consideration and the outcome data of the final studies were extracted by two reviewers independently from each other and were checked by the third reviewer.

Pharmacogenomics at the center of precision medicine: challenges and perspective in an era of Big Data.

Pharmacogenomics (PGx) is one of the core elements of personalized medicine. PGx information reduces the likelihood of adverse drug reactions and optimizes therapeutic efficacy. St Catherine Specialty Hospital in Zagreb/Zabok, Croatia has implemented a personalized patient approach using the RightMed Comprehensive PGx panel of 25 pharmacogenes plus Facor V Leiden, Factor II and MTHFR genes, which is interpreted by a special counseling team to offer the best quality of care.

Challenges in anesthesia personalization: resolving the pharmacogenomic puzzle.

Clinicians are witnessing differences in the doses required for induction and maintenance of anesthesia, as well as prolonged recovery in some patients. Predictable factors like patient characteristics, factors related to the procedure, pharmacological characteristics of anesthetics and adjunctive drugs, might explain some of the observed differences. However, the role of various polymorphisms of genes encoding for drugs' molecular targets, transporters and metabolic enzymes can have a significant impact on anesthesia outcome, too.

Mechanisms of Botulinum Toxin Type A Action on Pain.

Already a well-established treatment for different autonomic and movement disorders, the use of botulinum toxin type A (BoNT/A) in pain conditions is now continuously expanding. Currently, the only approved use of BoNT/A in relation to pain is the treatment of chronic migraines. However, controlled clinical studies show promising results in neuropathic and other chronic pain disorders.

Continuing war on pain: a personalized approach to the therapy with nonsteroidal anti-inflammatory drugs and opioids.

Successful pain management requires the delivery of analgesia with minimal risk of adverse drug reactions. Nonsteroidal anti-inflammatory drugs and opioids remain the mainstay of treatment for the majority of patients. Unfortunately, almost 50% of all patients experience inadequate pain relief and serious side effects.

Antinociceptive effect of botulinum toxin type A on experimental abdominal pain.

Visceral pain, especially in the abdominal region, represents one of the most common types of pain. Its chronic form is usually very hard to treat by conventional analgesic agents and adjuvants. We investigated the antinociceptive effect of botulinum toxin type A (BTX-A) in male Wistar rats in two models of visceral pain: peritonitis induced by intraperitoneal injection of 1% acetic acid and colitis induced by intracolonic instillation of 0.

Central action of peripherally applied botulinum toxin type A on pain and dural protein extravasation in rat model of trigeminal neuropathy.

Background: Infraorbital nerve constriction (IoNC) is an experimental model of trigeminal neuropathy. We investigated if IoNC is accompanied by dural extravasation and if botulinum toxin type A (BoNT/A) can reduce pain and dural extravasation in this model.

Methodology/principal Findings: Rats which developed mechanical allodynia 14 days after the IoNC were injected with BoNT/A (3.

Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: bilateral effect after unilateral injection.

We investigated antinociceptive activity of botulinum toxin type A (BTX-A) in a model of diabetic neuropathic pain in rats. Male Wistar rats were made diabetic by a single intraperitoneal injection of streptozotocin (80mg/kg). Sensitivity to mechanical and thermal stimuli was measured with the paw-pressure and hot-plate test, respectively.

Central origin of the antinociceptive action of botulinum toxin type A.

Here we provide behavioural evidence for an axonal transport and the central origin of the antinociceptive effect of botulinum toxin type A (BTX-A). In rats we investigated the effectiveness of BTX-A on "mirror pain" induced by unilateral repeated intramuscular acidic saline injections (pH 4.0).

Lasting reduction of postsurgical hyperalgesia after single injection of botulinum toxin type A in rat.

A single injection of low doses of botulinum toxin type A (3.5 U/kg) completely abolished secondary mechanical hyperalgesia throughout its duration in a model of post surgical pain after gastrocnemius incision in rat.

Lack of anti-inflammatory effect of botulinum toxin type A in experimental models of inflammation.

Botulinum toxin type A (BTX-A) has a long-lasting antinociceptive activity and less clear effect on inflammation. It was proposed that these two effects share the same mechanism--the inhibition of neurotransmitter exocytosis from peripheral nerve endings. However, till now possible anti-inflammatory action of BTX-A did not evoke much attention.

[Botulinum toxin type A and cholinergic system].

Anaerobic bacterium Clostridium botulinum produces seven different serotypes of botulinum neurotoxins (A-G), which specifically act at the peripheral cholinergic nerve terminals blocking the release of acethylcholine. Primary site of action of botulinum toxin type A (BT-A) is neuromuscular end plate where it specifically cleaves SNAP-25, one of the proteins necessary for neuroegzocytosis. The consequence is long-lasting muscle paralysis.

Reduced brain antioxidant capacity in rat models of betacytotoxic-induced experimental sporadic Alzheimer's disease and diabetes mellitus.

It is believed that oxidative stress (OS) plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus (DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer's disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induced diabetic rats and STZ-intracerebroventricularly (STZ-icv) treated rats, in which antioxidant capacity (AC) against peroxyl (ORAC(-ROO) (*)) and hydroxyl (ORAC(-OH) (*)) free radicals (FR) was measured in three different brain regions: the hippocampus (HPC), the cerebellum (CB), and the brain stem (BS) by means of oxygen radical absorbance capacity (ORAC) assay. In the brain of both STZ-induced diabetic and STZ-icv treated rats decreased AC has been found demonstrating regionally specific distribution.

Influence of ethanol on the myorelaxant effect of diazepam in rats.

Interaction of ethanol with benzodiazepines can lead to enhanced therapeutic anxyolytic, sedative and hypnotic effects but can also augment unwanted effects such as drowsiness, confusion, amnesia and impaired coordination. In this study we investigated the interaction between ethanol and diazepam and its influence on muscle strength in rats using the grip-strength meter. Three doses of ethanol (0.

Antinociceptive effect of botulinum toxin type a in rat model of carrageenan and capsaicin induced pain.

Aim: To test antinociceptive properties of botulinum toxin type A (BTX-A) in rats with carrageenan- and capsaicin-induced pain and inflammation.

Methods: Pain was provoked with carrageenan (1%) or capsaicin (0.1%) injection into the plantar surface of the rat paw-pad.

The antidepressant activity of Hypericum perforatum L. measured by two experimental methods on mice.

The pharmacological approach to the treatment of depression includes a long-term employment of antidepressants, either in the form of monotherapy or as a combination of several antidepressants with various mechanisms of action. Hypericum perforatum L. (St.

Analgesic effect of caffeine and clomipramine: a possible interaction between adenosine and serotonin systems.

The goals of this study were to determine whether the nonselective adenosine receptor antagonist caffeine exerts an analgesic effect and to investigate the time-dependent influence of the selective serotonin reuptake inhibitor clomipramine on the action of caffeine. Results suggest a possible interaction between serotonin and adenosine systems, which may contribute to the analgesic action of drugs. Therefore, the hot-plate and formalin tests were employed in order to measure the response to painful thermic and chemical stimuli.