Trigeminal autonomic cephalalgias (TACs) comprise cluster headaches and are characterized 19 by unilateral neuralgiform headache attacks associated with autonomic responses and somatic 2 20 responses. An animal model for evaluating the anatomical basis of the TAC-like response is 21 not currently available. Twenty-five rats weighing 550-650 g were anaesthetized with 22 urethane. The TAC-like response was produced either by subcutaneous injection of formalin 23 into the unilateral facial cheek or by electrical stimulation of the unilateral intact trigeminal 24 nerve. The induced TAC-like response, which included ipsilateral common carotid arterial 25 flow (iCCAF) and other autonomic responses, was studied in intact nerves or after cutting 26 either the ipsilateral trigeminal nerve or the ipsilateral facial nerve. The formalin injections 27 produced concentration-dependent iCCAF increases accompanied by ipsilateral autonomic 28 responses of rhinitis-like nasal congestion, nasal mucus, meiosis, lacrimation, red eye, and 29 eyelid oedema. The formalin (5% or 10%, 0.5 cc)-induced responses were nearly abolished 30 by sectioning of either the facial or trigeminal nerve. The electrical stimulation (15 V, 60 Hz, 31 and 0.4 ms) of the intact trigeminal nerve or its ophthalmo-maxillary branch also produced 32 stimulation strength-dependent iCCAF increases as well as autonomic responses; however, 33 the electrical stimulation-induced iCCAF increases and other autonomic responses could still 34 be induced by electrical stimulation of the central but not the peripheral end of the 35 ophthalmo-maxillary branch (n = 8) or the trigeminal nerve (n = 2). Thus, an animal model 36 for inducing the TAC-like response by subcutaneous formalin injection into the rat facial 37 cheek was established. The TAC-like response could be sequentially mediated via the 38 afferent trigeminal nerve, trigeminal nucleus, dorsal facial nucleus, and efferent facial nerve.