Photophobia is a common and highly bothersome migraine-associated symptom, where light may cause discomfort and exacerbate headache pain. Calcitonin gene-related peptide (CGRP) may be involved in nociceptive signalling during photophobia. In clinical provocation studies, intravenous CGRP induces both migraine attacks and photophobia. Animal studies attempting to model this have used intraperitoneal or intracranial injections and behavioural tests requiring very high light intensities to provoke light-aversive behaviour, a surrogate for photophobia-like responses. Here, we evaluated the effects of intravenous CGRP on light aversion alongside periorbital sensitivity in naïve rats. Male and female Sprague Dawley rats received intravenous injections of 100 µg/kg human αCGRP or saline (n = 6–12/group). After 20 min, light aversion was assessed in an optimized light/dark box (LDB) test. The LDB was optimized by adding bedding material to minimize novelty-related anxiety. Following a washout period, the same rats were re-dosed and tested in either a dim/dark box (DDB) test or an open field test (OFT) to evaluate anxiety in the absence of bright light. Cephalic allodynia, used as an indicator of headache-like pain, was assessed with von Frey measurements. CGRP-injected rats of both sexes spent significantly less time in the bright compartment of the LDB than controls. This avoidance was absent in the DDB test, and no CGRP-related effect was seen in the OFT, indicating that the effect was light-specific rather than anxiety-based. CGRP also significantly increased periorbital sensitivity, which was not seen following saline injection. Housing conditions and test order influenced outcomes, with female rats seemingly most affected. Grouping animals by treatment and using naïve rats for von Frey appeared to provide the most consistent results. Intravenous CGRP induced light aversion in both male and female rats, supported by a lack of effect in complementary anxiety tests. The same dose also induced cephalic allodynia, suggestive of headache-like pain. These findings show parallels to clinical provocation studies and highlight the translational potential of this intravenous model for studying migraine-related photophobia-like behaviour. Moreover, the study underscores that housing and test order can strongly influence behavioural outcomes, emphasizing the importance of experimental design in preclinical migraine research. The online version contains supplementary material available at 10.1186/s10194-026-02278-2.

Endothelin-1 (ET-1) overactivity has been implicated as a factor contributing to glaucomatous neuropathy, and it has been utilized in animal models of retinal ischemia. The functional effects of long-term ET-1 exposure and possible compensatory mechanisms have, however, not been investigated. This was therefore the purpose of our study. ET-1 was delivered into rat eyes via a single intravitreal injection of 500 µM or via transgene delivery using an adeno-associated viral (AAV) vector. Retinal function was assessed using electroretinography (ERG) and the retinal expression of potentially compensatory genes was evaluated by means of qRT-PCR. Acute ET-1 delivery led to vasoconstriction and a significant reduction in the ERG response. AAV–ET-1 resulted in substantial transgene expression and ERG results similar to the acute ET-1 injections and comparable to other models of retinal ischemia. Compensatory changes were observed, including an increase in calcitonin gene-related peptide (CGRP) gene expression, which may both counterbalance the vasoconstrictive effects of ET-1 and provide neuroprotection. This chronic ET-1 ischemia model might be especially relevant to glaucoma research, mimicking the mild and repeated ischemic events in patients with long-term vascular dysfunction. The compensatory mechanisms, and particularly the role of vasodilatory CGRP in mitigating the retinal damage, warrant further investigation with the aim of evaluating new therapeutic strategies.

Background: Opioids are considered ideal for managing moderate to severe post-operative pain in laboratory rodents, with buprenorphine being one of the most commonly used analgesics in rats. A long-acting buprenorphine formulation would be highly beneficial to avoid frequent dosing of postoperative animals; however, buprenorphine depot formulations developed for animal use are not available in Europe. The purpose of the present study was therefore to evaluate the effects in rats of a long-acting subcutaneous depot injection with buprenorphine developed for humans (Buvidal). Results: Buvidal was evaluated in male Sprague Dawley rats alongside conventional short-acting buprenorphine (Temgesic) delivered subcutaneously and orally, a non-opioid analgesic (carprofen), and controls (saline). All three buprenorphine formulations resulted in significantly reduced mechanical sensitivity when assessed in pain-free, naïve rats using the von Frey pressure test at early time points (3–6 h), whereas carprofen and saline had no effect on tactile sensitivity. In a hypersensitivity model of cephalic allodynia, the hypoalgesic effect of Buvidal lasted beyond 24 h. Plasma concentrations support prolonged drug exposure following administration of the long-acting formulation, and levels exceeding 1 ng/mL were observed during periods of reduced tactile sensitivity. No significant effect on locomotor activity was found in an open field test following buprenorphine administration. Transient pica-like chewing behaviour and reduced alertness were observed in some buprenorphine-treated animals during the first hours after drug administration. Conclusions: The human slow-release buprenorphine formulation Buvidal produced sustained systemic exposure and prolonged hypoalgesic effects in male rats, as demonstrated in the cephalic hypersensitivity model, consistent with depot release kinetics. These results show that Buvidal is pharmacologically active in rats and may represent a potential approach for achieving sustained buprenorphine effects in experimental studies requiring prolonged opioid analgesia where rodent-specific formulations are unavailable, although further evaluation of safety, dosing, and generalizability is required.