Neuroinflammation in the prefrontal-amygdala-hippocampus network is associated with maladaptive avoidance behaviour.

Maladaptive avoidance behaviour is often observed in patients suffering from anxiety and trauma- and stressor-related disorders. The prefrontal-amygdala-hippocampus network is implicated in learning and memory consolidation. Neuroinflammation in this circuitry alters network dynamics, resulting in maladaptive avoidance behaviour. The two-way active avoidance test is a well-established translational model for assessing avoidance responses to stressful situations. While some animals learn the task and show adaptive avoidance (AA), others show strong fear responses to the test environment and maladaptive avoidance (MA). Here, we investigated if a distinct neuroinflammation pattern in the prefrontal-amygdala-hippocampus network underlies the behavioural difference observed in these animals. Wistar rats were tested 8 times and categorized as AA or MA based on behaviour. Brain recovery followed for the analysis of neuroinflammatory markers in this network. AA and MA presented distinct patterns of neuroinflammation, with MA showing increased astrocyte, EAAT-2, IL-1ß, IL-17 and TNF-ɑ in the amygdala. This neuroinflammatory pattern may underlie these animals' fear response and maladaptive avoidance. Further studies are warranted to determine the specific contributions of each inflammatory factor, as well as the possibility of treating maladaptive avoidance behaviour in patients with psychiatric disorders with anti-inflammatory drugs targeting the amygdala.

Effect of the C-terminus of murine S100A9 protein on experimental nociception.

Calcium-binding protein S100A9 induces antinociception in mice evaluated by the writhing test. Similarly, a peptide identical to the C-terminus of murine S100A9 (mS100A9p) inhibits the hyperalgesia induced by jararhagin, a metalloprotease. Thus, we investigated the effect of mS100A9p on different models used to evaluate nociception. mS100A9p induced a dose-dependent inhibitory effect on the writhing test, and on mechanical hyperalgesia induced by carrageenan. mS100A9p inhibited thermal hyperalgesia induced by carrageenan. mS100A9p did not modify the nociceptive response in hot plate or tail-flick tests. These data demonstrate that the C-terminus of S100A9 protein interferes with control mechanisms of inflammatory pain.

Hemopressin: a novel bioactive peptide derived from the alpha1-chain of hemoglobin.

Hemopressin (PVNFKFLSH), a novel bioactive peptide derived from the alpha1-chain of hemoglobin, was originally isolated from rat brain homogenates. Hemopressin causes hypotension in anesthetized rats and is metabolized in vivo and in vitro by endopeptidase 24.15 (EP24.15), neurolysin (EP24.16), and angiotensin-converting enzyme (ACE). Hemopressin also exerts an antinociceptive action in experimental inflammatory hyperalgesia induced by carrageenin or bradykinin via a mechanism that is independent of opioids. These findings suggest that this peptide may have important regulatory physiological actions in vivo.

Hemopressin: a novel bioactive peptide derived from the alpha1-chain of hemoglobin

Hemopressin (PVNFKFLSH), a novel bioactive peptide derived from the alpha1-chain of hemoglobin, was originally isolated from rat brain homogenates. Hemopressin causes hypotension in anesthetized rats and is metabolized in vivo and in vitro by endopeptidase 24.15 (EP24.15), neurolysin (EP24.16), and angiotensin-converting enzyme (ACE). Hemopressin also exerts an antinociceptive action in experimental inflammatory hyperalgesia induced by carrageenin or bradykinin via a mechanism that is independent of opioids. These findings suggest that this peptide may have important regulatory physiological actions in vivo.

Antinociceptive action of hemopressin in experimental hyperalgesia.

Endogenous hemorphins, derived from degradation of the beta-chain of hemoglobin, lower arterial blood pressure and exert an antinociceptive action in experimental models of nociception. Hemopressin, derived from the alpha-chain of hemoglobin, also decreases blood pressure, but its effects on pain have not been studied. In this work, we examined the influence of hemopressin on inflammatory pain. Hemopressin reverted the hyperalgesia induced by either carrageenin or bradykinin when injected concomitantly or 2.5 h after the phlogistic agents. Hemopressin administered systemically also reverted the hyperalgesia induced by carrageenin. Naloxone did not prevent the antinociceptive action of this peptide. These data suggest that hemopressin inhibits peripheral hyperalgesic responses by mechanisms independent of opioid receptor activation.