Resultados preclínicos de cannabinoides y dolor (algunos) / Some preclinical results of cannabinoids and pain

El papel del sistema endocannabinoide en la modulación de la nocicepción y en la interpretación de estas señales se conoce desde mediados del siglo pasado. Los trabajos desarrollados desde entonces han permitido profundizar en los mecanismos de acción implicados y así poder sintetizar diversos fármacos capaces de modular estas señales. Estos fármacos pueden ser agonistas, dirigidos a activar directamente receptores cannabinoides, pero pueden igualmente ser sustancias que modulen las enzimas encargadas de las síntesis y degradación de los endocannabinoides. Farmacológicamente se están estudiando, además, otras sustancias presentes en la planta Cannabis sativa, así como derivados sintéticos obtenidos a partir de estas, que pueden unirse, además de a los receptores antes mencionados, a otros tipos de receptores implicados en la fisiología de la nocicepción. Los resultados obtenidos hasta el momento demuestran eficacia en múltiples modelos animales de dolor, tanto agudo como crónico, tanto nociceptivo como neuropático, y abren vías de investigación para el tratamiento farmacológico del dolor crónico.(AU)

The role of the endocannabinoid system in the modulation of nociception and in the interpretation of those signals in known since the middle of the last century. The work carried out since then has made possible to better understand mechanisms of action involved and to synthesize different drugs able to modulate these signals. These drugs can be agonists, aimed at directly activating cannabinoid receptors, or substances that modulate the enzymes responsible for the synthesis and degradation of endocannabinoids. Pharmacologically, other substances present in the Cannabis sativa plant are also being studied, as well as synthetic derivatives obtained from these, which can bind, in addition to the aforementioned receptors, to other types of receptors involved in the physiology of the nociception. Results obtained to date demonstrate efficacy in multiple animal models of pain, both acute and chronic, both nociceptive and neuropathic, and offer new of research lines for the pharmacological treatment of chronic pain.(AU)

Behavior and electrophysiology studies of the peripheral neuropathy induced by individual and co-administration of paclitaxel and oxaliplatin in rat.

AIMS: Antitumor agents, as taxanes and platinum compounds, induce peripheral neuropathies which can hamper their use for cancer treatment. The study of chemotherapy-induced neuropathies in humans is difficult because of ethical reasons, differences among administration protocols and intrinsic characteristics of patients. The aim of the present study is to compare the neuropathic signs induced by individual or combined administration of paclitaxel and oxaliplatin. MAIN METHODS: Oxaliplatin and paclitaxel were administered individually and combined to induce peripheral neuropathy in rats, sensory neuropathic signs were assessed in the hind limbs and orofacial area. The in vitro skin-saphenous nerve preparation was used to record the axonal activity of Aδ sensory neurons. KEY FINDINGS: Animals treated with the combination developed mechanical allodynia in the paws and muscular hyperalgesia in the orofacial area, which was similar to that in animals treated with monotherapy, the latter also developed cold allodynia in the paws. Aδ-fibers of the rats treated with the combination were hyperexcited and presented hypersensitivity to pressure stimulation of the innervated skin, also similar to that recorded in the fibers of the animals treated with monotherapy. SIGNIFICANCE: Our work objectively demonstrates that the combination of a platinum compound with a taxane does not worsen the development of sensorial neuropathies in rats, which is an interesting data to take into account when the combination of antitumor drugs is necessary. Co-administration of antitumor drugs is more effective in cancer treatment without increasing the risk of the disabling neuropathic side effects.

Chronic pain and cannabinoids. Great expectations or a christmas carol.

The discovery of the endocannabinoid system nearly three decades ago generated great interest among pain scientists. Moreover, its analogy with the opioid system in terms of evolutionary preservation, tissue localization and analgesic activity enabled a vast new field for the development of medicines addressed to those types of pain that still nowadays are difficult to manage. However, the main disadvantage that hampers the use of cannabinergic drugs as analgesics is their identification with recreational use, besides their psychotomimetic actions. Pain has traditionally been classified attending to the ailment duration (acute or chronic) and drugs are used according to the intensity of the pain to treat, but it is also important to target the mechanism involved despite the intensity or duration of pain. The present chapter reviews the study and use of cannabinoids attending separately to four classic types of pain: nociceptive, inflammatory, neuropathic and oncological, considering basic research (pain animal models) as well as clinical practice.