18 kDa Translocator protein (TSPO) is upregulated in rat brain after peripheral nerve injury and downregulated by diroximel fumarate.

Neuroimmune signaling is a key process underlying neuropathic pain. Clinical studies have demonstrated that 18 kDa translocator protein (TSPO), a putative marker of neuroinflammation, is upregulated in discrete brain regions of patients with chronic pain. However, no preclinical studies have investigated TSPO dynamics in the brain in the context of neuropathic pain and in response to analgesic treatments.

Persistent inflammatory pain is linked with anxiety-like behaviors, increased blood corticosterone, and reduced global DNA methylation in the rat amygdala.

Chronic pain increases the risk of developing anxiety, with limbic areas being likely neurological substrates. Despite high clinical relevance, little is known about the precise behavioral, hormonal, and brain neuroplastic correlates of anxiety in the context of persistent pain. Previous studies have shown that decreased nociceptive thresholds in chronic pain models are paralleled by anxiety-like behavior in rats, but there are conflicting ideas regarding its effects on the stress response and circulating corticosterone levels.

HO-CO pathway activation may be associated with hippocampal μ and δ opioid receptors in inhibiting inflammatory pain aversiveness and nociception in WT but not NOS2-KO mice.

Carbon monoxide (CO) and nitric oxide (NO) modulate inflammatory nociception and anxiety. We evaluate whether treatments with a heme oxygenase-1 (HO-1) inducer (CoPP) or a carbon monoxide-releasing molecule (CORM-2) are capable of inhibiting inflammatory pain aversiveness in wild type (WT) and inducible nitric oxide synthase-knock out (NOS2-KO) mice with persistent inflammation and its relationship with μ- (MOR) and δ- (DOR) opioid receptors. WT and NOS2-KO male mice with complete Freund's adjuvant (CFA) injected into the hind paw were evaluated in the von Frey and the escape-avoidance paradigm (PEAP) tests, at 10 days, before and after the treatment with CORM-2 (5 mg/kg) or CoPP (2.

Sepsis-induced encephalopathy impairs descending nociceptive pathways in rats.

Sepsis-associated encephalopathy (SAE) is a significant problem in patients with sepsis, and it is associated with a decrease in cognitive and sensitivity capability induced by systemic inflammation. SAE is implicated in reversible brain damage of several regions related to cognition, emotion, and sensation; however, it is not well established if it could affect brain regions associated with nociceptive modulation. Here were evaluated the nociceptive thresholds in rats with systemic inflammation induced by cecal ligation puncture (CLP).

Neuroinflammation in the NTS is associated with changes in cardiovascular reflexes during systemic inflammation.

Background: Lipopolysaccharide (LPS)-induced systemic inflammation (SI) is associated with neuroinflammation in the brain, hypotension, tachycardia, and multiple organs dysfunctions. Considering that during SI these important cardiovascular and inflammatory changes take place, we measured the sensitivity of the cardiovascular reflexes baroreflex, chemoreflex, and Bezold-Jarisch that are key regulators of hemodynamic function. We also evaluated neuroinflammation in the nucleus tractus solitarius (NTS), the first synaptic station that integrates peripheral signals arising from the cardiovascular and inflammatory status.

The Effects of Cobalt Protoporphyrin IX and Tricarbonyldichlororuthenium (II) Dimer Treatments and Its Interaction with Nitric Oxide in the Locus Coeruleus of Mice with Peripheral Inflammation.

Heme oxygenase 1 (HO-1) and carbon monoxide were shown to normalize oxidative stress and inflammatory reactions induced by neuropathic pain in the central nervous system, but their effects in the locus coeruleus (LC) of animals with peripheral inflammation and their interaction with nitric oxide are unknown. In wild-type (WT) and knockout mice for neuronal (NOS1-KO) or inducible (NOS2-KO) nitric oxide synthases with inflammatory pain induced by complete Freund's adjuvant (CFA), we assessed: 1) antinociceptive actions of cobalt protoporphyrin IX (CoPP), an HO-1 inducer; 2) effects of CoPP and tricarbonyldichlororuthenium(II)dimer (CORM-2), a carbon monoxide-liberating compound, on the expression of HO-1, NOS1, NOS2, CD11b/c, GFAP,and mitogen-activated protein kinases (MAPK)in the LC. CoPP reduced inflammatory pain in different time-dependent manners in WT and KO mice.

Enhanced expression of heme oxygenase-1 in the locus coeruleus can be associated with anxiolytic-like effects.

Some researchers have shown that carbon monoxide (CO) plays a role in emotional behavior modulation through intracellular 3'-5'-guanosine monophosphate mechanisms in the locus coeruleus (LC). In fact, the LC region has a high expression of the heme-oxygenase (HO) enzymes, which are responsible for the production of CO. However, the physiological mechanism by which the HO-CO pathway participates in the modulation of emotional responses in the LC still needs clarification.