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Neuropathic pain is still a serious and unsolved health problem. Activation of α7 nicotinic acetylcholine receptor (α7nAChR) is known to modulate neuropathic pain by inhibiting microglial activation and BDNF/TrkB/KCC2 signaling. We previously identified that trifluoro-icaritin (ICTF) has an attenuated effect on spared nerve injury (SNI)-induced neuropathic pain, but its potential mechanisms remain unknown. Here, the pain-related behaviors were determined by paw withdrawal threshold (PWT), CatWalk gait analysis, rotarod test, open field test and elevated plus maze test. The expression of pain-related signal molecules was evaluated by Western blot and immunofluorescence staining. The results showed that ICTF (5.0 mg/kg, i.p.) successfully relieved SNI-induced mechanical allodynia and anxiety-like behavior, we subsequently found there existed either positive or negative correlation between mechanical allodynia and gait parameters or rotating speed following ICTF treatment. Moreover, ICTF not only enhanced the expression of spinal α7nAChR, KCC2, CD206 and IL-10, but also decreased the levels of spinal BDNF, TrkB, CD11b, Iba-1, CD40 and IL-1β in SNI rats. Conversely, α7nAChR antagonist α-Bgtx (I.T.) effectively reversed the inhibitory effects of ICTF on SNI rats, resulting in a remarkable improvement of mechanical allodynia, activation of microglia. and suppression of α7nAChR-mediated BDNF/TrkB/KCC2 signaling. Additionally, exogenous BDNF (I.T.) dramatically abrogated both blockade of BDNF/TrkB/KCC2 cascade and alleviation of mechanical allodynia by ICTF treatment. Altogether, the study highlighted that ICTF could relieve SNI-induced neuropathic pain by suppressing microglial activation via α7nAChR-mediated inhibition of BDNF/TrkB/KCC2 signaling in the spinal cord, suggesting that ICTF may be served as a possible painkiller against neuropathic pain.

The Headache and Neurologic Deficits with cerebrospinal fluid Lymphocytosis syndrome (HaNDL) is a rare, benign and self-limited entity of unknown cause, diagnosed by exclusion. It usually presents with neurological deficits such as hemiparesthesia, dysphasia and hemiparesis. However, seizures are not usually associated with the clinical spectrum of this syndrome. Here we report a case of a 35 year-old male patient with multiple episodes of moderate-severe headaches with transient hemiparesthesia, dysarthria, confusion, visual hallucinations, disinhibited behavior, and a bilateral tonic-clonic seizure. HaNDL diagnosis was made after clinical improvement and CSF evolution. Clinicians should consider HaNDL syndrome in patients presenting with headache, seizures, and confusion, when all other etiologies are ruled out.

We hypothesized that unilateral leg pain following surgical treatment of lumbar disc herniation (LDH) is associated with an increase in the glucose metabolism of the contralateral thalamus.

Opioids are often used to manage postoperative pain. Non-narcotic alternatives have increasingly been used to reduce opioid usage. We conducted an open-label randomized non-inferiority clinical trial to compare non-opioid to opioid therapy for pain management after nephrolithiasis surgery.

Migraine and depression often coexist and constitute an important clinical problem. Both disorders are associated with the necessity of chronic treatment, and their mutual coexistence contributes to the phenomenon of drug resistance. Influencing the functioning of patients, they also cause numerous social consequences – affecting the quality of life and achievement of personal goals of patients. This review presents factors that may explain the common pathomechanisms of depression and migraine. Structural and functional disturbances of the central nervous system (CNS), disturbances in the neurotransmitter systems, inflammatory theories, hormonal disturbances, as well as a possible genetic basis were taken into account. Due to the fact that both depression and migraine have a multifactorial etiology and at the present stage of scientific research it is difficult to clearly determine which factor is the most important, such a broad overview has been presented. It is also difficult to determine which of the above-mentioned factors, well documented in international studies, only coexist, and which of them may have a cause-and-effect relationship in the described disorders. Further research into the comorbidity and causes of migraine and depression seems to be worth considering.

Gastroduodenal symptoms are highly prevalent, with underlying sensorimotor dysfunction contributing in many patients. Common symptoms include early satiation, postprandial fullness, epigastric bloating, pain or burning, nausea and vomiting, which collectively affect over 7% of adults. However, the clinical evaluation of these symptoms remains challenging, with current tests of gastric function remaining limited in their ability or availability to separate specific patient subgroups or guide-targeted care.

Osteoarthritis is a common and severe, multifactorial disease with a well-established genetic component. However, little is known about how genetics affect disease progression, and thereby the need for joint placement. Therefore, we aimed to investigate whether the genetic associations of knee and hip osteoarthritis differ between patients treated with joint replacement and patients without joint replacement.

As the ability to capture single-cell expression profiles has grown in recent years, neuroscientists studying a wide gamut of brain regions have discovered remarkable heterogeneity within seemingly related populations (Saunders et al., 2018a; Zeisel et al., 2015). These "molecular subtypes" have been demonstrated even within brain nuclei expressing the same neurotransmitter (Saunders et al., 2018a; Poulin et al., 2020; Ren et al., 2019; Okaty et al., 2020). Recently, dopamine (DA) neurons of the substantia nigra pars compacta (SNc) and adjacent ventral tegmental area (VTA) have been revealed to be diverse not only when comparing between these two dopaminergic nuclei, but within them, and with the distribution of identified subtypes often agnostic to traditional neuroanatomical boundaries (Saunders et al., 2018a; Hook et al., 2018; Kramer et al., 2018; La Manno et al., 2016; Poulin et al., 2014; Tiklova et al., 2019; Poulin et al., 2018). Such molecularly defined subpopulations have been the subject of several recent studies. Investigations of these subtypes have ultimately unveiled many distinctive properties across several domains, such as their axonal projections and functional properties (Poulin et al., 2018; Wu et al., 2019; Pereira Luppi et al., 2021; Evans et al., 2017; Evans et al., 2020). These key differences between subtypes have begun to corroborate the biological relevance of DA neuron taxonomic schemes. We hypothesize that these putative molecular subtypes, with their distinctive circuits, could shed light on the wide variety of dopamine-related symptoms observed across several diseases including depression, chronic pain, addiction, and Parkinson's Disease. While it is difficult to reconcile how a single neurotransmitter can be involved in so many seemingly unrelated phenotypes, one solution could be the existence of several individual dopaminergic pathways serving different functions, with molecular subtypes serving as distinct nodes for these pathways. Indeed, this conceptual framework is already the dogma for anatomically distinct DA pathways, including the mesocortical, mesolimbic and mesostriatal pathways (Bjorklund & Dunnett, 2007). Here, we discuss our existing knowledge of DA neuron subtypes and attempt to provide a roadmap for how their distinctive properties can provide novel insights into the motor symptoms of Parkinson's disease (PD) (Fig. 1A). By exploring the differences between molecular subtypes and correlating this to their relative degeneration within the SNc, we may gain a deeper understanding of the cell-intrinsic mechanisms underlying why some DA neurons degenerate more than others in PD. Similarly, by mapping the inputs, projections, and functions of individual subtypes, we may better understand their individual roles in the circuit-level dysfunction of dopaminergic diseases.

The present study investigated the involvement of mediodorsal thalamic (MD) GABA-A receptors in cetirizine/morphine-induced anti-allodynia using a rat model of neuropathic pain. To assess the importance of the prefrontal cortex (PFC) for chronic pain processing, its expression level changes of glial fibrillary acidic protein (GFAP) were measured following drug treatments. Each animal was subjected to chronic constriction of the sciatic nerve surgery simultaneously with the MD cannulation under stereotaxic surgery. The results showed that the administration of morphine (3-5mg/kg) or cetirizine (1-3mg/kg) produced significant analgesia in neuropathic rats. Systemic administration of cetirizine (2.5mg/kg) potentiated the analgesic response to a low and intolerance dose of morphine (3mg/kg). Intra-MD microinjection of muscimol, a selective GABA-A receptor agonist (0.005-0.01μg/rat), increased the cetirizine/morphine-induced anti-allodynia, while muscimol by itself did not affect neuropathic pain. The neuropathic pain was associated with the increased PFC expression level of GFAP, suggesting the impact of chronic pain on PFC glial management. Interestingly, the anti-allodynia was associated with a decrease in the PFC expression level of GFAP under the drugs' co-administration. Thus, cetirizine has a significant potentiating effect on morphine response in neuropathic pain via interacting with the MD GABA-A receptors. It seems that neuropathic pain affects the prefrontal cortex GFAP signaling pathway. In clinical studies, these findings can be considered to create a combination therapy with low doses of GABA-A receptor agonist plus cetirizine and morphine to manage neuropathic pain.