Various models and examples can help identify responses to noxious stimuli that do not necessarily involve pain. Such responses occur (1) in organisms with either no nervous system or a nervous system so simple that scientists believe the organism is not capable of affect; (2) in mammals whose forebrains are not receiving input from the periphery; and (3) in humans whose pain has been suppressed (e.g., by analgesics/anesthetics).
Autonomic responses to noxious stimuli.In adult humans, postoperative cortisol output is undiminished by analgesics that successfully treat the reported pain (Schulze et al. 1988 cited by Lee et al. 2005; Dahl et al. 1992; see also Carrasco and Van de Kar 2003). Sympathetic responses such as tachycardia, hypertension, and pupil dilation occur in response to noxious stimuli in decerebrate rats and dogs (Sherrington 1906, reviewed in Sivarao et al. 2007).
Simple avoidance responses.Nonlearned avoidance responses are present in even simple single-celled organisms and require no affect (Rolls 2000; Tye 2007; Winkielman et al. 2005). The withdrawal of body parts (e.g., limbs, tails) from noxious stimuli also occurs in decerebrate cats (Sherrington 1906), and spinal-transected cats and rats in which connections to the brain are severed (e.g., Grau et al. 1998). In spinally transected cats, pinching or clamping the tail promotes stepping movements of the hindlimbs (Lovely et al. 1986), as though simple locomotory escape movements can occur even without pain. Some learned avoidance responses (e.g., classically conditioned withdrawal) have even been observed in the sea slug Aplysia (reviewed by Allen 2004). Other research reveals the instrumental learning of avoidance responses normally associated with pain with no possible involvement of the brain: spinally transected rats learn to keep their limbs withdrawn for longer periods of time if doing so will terminate the insult (Grau et al. 1998).
Other behavioral responses.Turning of the head and neck toward the noxious stimulus, some vocalization, and the licking of affected paws may occur in decerebrate animals (Baliki et al. 2005; King et al. 2003; Sherrington 1906).
Other responses.Cerebral blood flow increases during venipuncture in human fetuses as young as 16 weeks gestational age, even though the thalamocortical connections required for nociceptive input to reach the cortex have not developed (Lee et al. 2005). Isoflurane-anesthetized rats show activation in several forebrain regions (e.g., cingulate and insular cortices) in response to noxious stimuli applied to a paw (Hess et al. 2007).a
The responses listed here are unreliable as indices of pain when attemtpting to assess whether a particular species or stage of development can experience pain and not just nociception. To make this assessment, stronger evidence is required. The absence of this stronger evidence is what fuels debates about nonmammalian vertebrates (see Box 1-4 and text). In intact animals, however, these nociceptive responses do often play an important and significant role in pain assessment (see Chapter 3).
From: 1, Pain in Research Animals: General Principles and Considerations
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