Ovarian hormones play an important role in pain perception, and are responsible, at least in part, for the pain threshold differences between the sexes. Modulation of pain and its perception are mediated by neurochemical changes in several pathways, affecting both the central and peripheral nervous systems. One of the most studied neurotransmitters related to pain disorders is serotonin. Estrogen can modify serotonin synthesis and metabolism, promoting a general increase in its tonic effects. Studies evaluating the relationship between serotonin and disorders such as irritable bowel syndrome, fibromyalgia, migraine, and other types of headache suggest a clear impact of this neurotransmitter, thereby increasing the interest in serotonin as a possible future therapeutic target. This literature review describes the importance of substances such as serotonin and ovarian hormones in pain perception and illustrates the relationship between those two, and their direct influence on the presentation of the aforementioned pain-related conditions. Additionally, we review the pathways and receptors implicated in each disorder. Finally, the objective was to stimulate future pharmacological research to experimentally evaluate the potential of serotonin modulators and ovarian hormones as therapeutic agents to regulate pain in specific subpopulations.

Tryptophan (TRP) is an essential, aromatic amino acid catabolized by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) enzymes into kynurenine. The IDO enzyme is expressed in peripheral tissues and the central nervous system. Another enzyme of interest in the kynurenine signaling pathway is kynurenine 3-monooxygenase (KMO). The purpose of this review is to discuss the role of TRP and the kynurenine signaling pathway in different chronic pain patients. The IDO-1, IDO-2, and KMO enzymes and the kynurenine metabolite have been shown to be involved in the pathogenesis of neuropathic pain and other painful conditions (migraine, cluster headache, etc.) as well as depressive behavior. We highlighted the analgesic potential of novel agents targeting the enzymes of the kynurenine signaling pathway to explore their efficacy in both future basic science and transitional studies. Upcoming studies conducted on animal models will need to take into consideration the differences in TRP metabolism between human and non-human species. Since chronic painful conditions and depression have common pathophysiological patterns, and the kynurenine signaling pathway is involved in both of them, future clinical studies should aim to have outcomes targeting not only pain, but also functionality, mood changes, and quality of life.

Introduction: Neuropathic pain is a chronic condition that significantly affects the quality of life of millions of people globally. Most of the pharmacologic treatments currently in use demonstrate modest efficacy and over half of all patients do not respond to medical management. Hence, there is a need for new, efficacious drugs. Evidence points toward voltage-gated sodium channels as a key target for novel analgesics. Area covered: The role of voltage-gated sodium channels in pain pathophysiology is illuminated and the preclinical and clinical data for new sodium channel blockers and toxin-derived lead compounds are examined. The expansion of approved sodium channel blockers is discussed along with the limitations of current research, trends in drug development, and the potential of personalized medicine. Expert opinion: The transition from preclinical to clinical studies can be difficult because of the inherent inability of animal models to express the complexities of pain states. Pain pathways are notoriously intricate and may be pharmacologically modulated at a variety of targets; it is unlikely that action at a single target could completely abolish a pain response because pain is rarely unifactorial. Combination therapy may be necessary and this could further confound the discovery of novel agents.

Corticosteroids have played a standard role in the multimodal pain management in the treatment of chronic spinal pain (cervical and lumbar) and osteoarthritis pain over the past three decades. In this review we discuss different types of injectable steroids that are mainly used for injection into the epidural space (for the treatment of radicular back and neck pain), and as intraarticular injections for different types of osteoarthritis related pain conditions. Furthermore, we discuss different approaches taken for epidural corticosteroid injections and spinal surgical rates when injections fail to resolve painful conditions, as well as the possibility of using local anesthetics alone for neuraxial injections, instead of in combination with corticosteroids. While we present some beneficial effects of newly available treatment options for low back pain and osteoarthritis pain, such as use of PRP and hyaluronic acid, corticosteroids remain important considerations in the management of these chronic pain conditions.

It is estimated that the total annual financial cost for pain management in the U.S. exceeds 100 billion dollars. However, when indirect costs are included, such as functional disability and reduction in working hours, the cost can reach more than 300 billion dollars. In chronic pain patients, the role of pharmacogenetics is determined by genetic effects on various pain types, as well as the genetic effect on drug safety and efficacy. In this review article, we discuss genetic polymorphisms present in different types of chronic pain, such as fibromyalgia, low back pain, migraine, painful peripheral diabetic neuropathy and trigeminal neuralgia. Furthermore, we discuss the role of CYP450 enzymes involved in metabolism of drugs, which have been used for treatment of chronic pain (amitriptyline, duloxetine, opioids, etc.). We also discuss how pharmacogenetics can be applied towards improving drug efficacy, shortening the time required to achieve therapeutic outcomes, reducing risks of side effects, and reducing medical costs and reliance upon polypharmacy.