It has been established that central sensory and affective pain processes share common sensory mechanisms in the periphery: A-delta and C-fibers serve as tissue-trauma transducers (nociceptors) for both types of pain process: the chemical products of inflammation sensitize these nociceptors, and peripheral neuropathic mechanisms such as ectopic firing excite both processes (Bromm & Desmedt, 1995). Differentiation of sensory and effective processing begins at the dorsal horn of the spinal cord, with sensory transmission following spinothalamic pathways, and transmission destined for affective processing taking place in spinoreticular pathways.
Nociceptive centripetal transmission involves both the spinoreticular and the spinothalamic tracts (Bromm & Desmedt, 1995). The spinoreticular tract contains somatosensory and viscerosensory afferent pathways that arrive at different levels of the brain stem. Axons of the spinoreticular pathways have active sites resembling those of spinothalamic-tract neurons that project to the medial thalamus, and like their spinothalamic counterparts, transmit tissue-injury information. It has been shown that most spinoreticular neurons carry nociceptive signals and that many of them respond preferentially to noxious input (Bromm & Desmedt, 1995).
The processing of pain signals to produce a response starts in the reticulocortical pathways. There are four different extrathalamic afferent pathways that project to the neocortx: the dorsal noradrenergic bundle (DNB), originating in the locus coeruleus (LC); the serotonergic fibers that arise in the dorsal and median raphe nuclei; the dopaminergic pathways of the ventral tegmental tract that originate from the nucleus basalis of the substantia nigra; and the acetylcholinergic neurons that arise principally from the nucleus basalis of the substantia innominata (Broom & Desmedt, 1995). Of these four extrathalamic pathways, the noradenergic pathway links most closely to negative emotional state (for review, see Gray, 1982, 1987). The set of structures receiving projections from these pathways correspond to the classic definition of the limbic brain (Bromm & Desmedt, 1995).
Although there are many processes that are involved in the feeling of emotion during pain, I will only talk about the role of the central noradrenergic processes in my discussion of emotion and pain, since this system is link most closely to negative emotional state. The noradrenergic system comprised of two central noradrenergic pathways: the dorsal and ventral noradrenergic bundles.
The pontine nucleus known as the locus coeruleus (LC) lies bilaterally near the wall of the fourth ventricle. The locus contains three major projection: ascending, descending, and cerebellar. The dorsal noradrenergic bundle (DNB) constitute the ascending pathways; it projects form the LC throughout the limbic brain and to all the neocortex, accounting for about 70% of all brain norepinephrine (see diagram 2) (Bromm & Desmedt, 1995). The LC is the central source of the majority of central noradrenergic fibers in the spinal cord, hypothalamus, thalamus, and the hippocampus (for review, see Levitt and Morre, 1979; Aston-Jones et al., 1985), in addition to its projections to the limbic cortex and neocortex.
The LC is the relay center for receiving and transmitting sensory information that serve to warn the individual of harm. Nociception increase activity in neurons of the LC, and excitation of neurons in the LC appears to be responding to the nociception (Bromm & Desmedt, 1995). Studies in animals have demonstrated that this response does not require cognitively mediated attention control, since it occurs when the animal is anesthetized (for review, see Korf et al. 1974; Stone 1975; Morilak et al. 1987; Svensson 1987). An experiment done by Foote et al. in 1983, shows that slow, tonic spontaneous activity at the LC in rats changed under anesthesia upon noxious stimulation. Other studies demonstrated that experimentally induced phasic LC activation result in alarm and fear response in primates, and lesions of the LC eliminate normal heart rate increases in response to threatening stimulus (Bromm & Desmedt, 1995).
Furthermore, invasive studies confirm the connection between LC activity and threat. Studies shows that direct activation of the DNB and associated limbic structures in laboratory animals produces a sympathetic nervous response and elicits emotional behaviors (e.g. defensive threat, fear, enhanced startle, freezing, and vocalization) (for review, see McNaughton & Mason 1980). This suggests that increased activity in these pathways corresponds to negative emotional arousal and behaviors appropriate to the situation. Thus, as a subjective experience, "the emotional quality of pain therefore seems to be most accurately described as awareness of immediate biological threat" (Bromm & Desmedt 1995).
The ventral noradrenergic bundle (VNB), like the DNB, is an ascending noradrenergic system; it enters the medial forebrain bundle. Neurons in the medullary reticular formation project to the hypothalamus via the VNB (for review, see Sumal et al. 1983; Bonica 1990). The medullary neuronal complexes also supply 90% of catecholaminergic innervation to the paraventricular hypothalamus via the VNB (for review, see Assenmacher et al. 1987).
The VNB is an important component for pain research because it innervates the hypothalamus. The hypothalamus regulates the anterior and posterior pituitary glands, the autonomic system, is involve in what is referred to as the four F’s (flight, fighting, feeding, and mating), and it is responsible for species specific behaviors. The noradrenergic axons in the VNB respond to painful stimuli as does the hypothalamus (for review, see Kanosue et al. 1984; Svensson 1987). It has also been shown that nociception-transmitting neurons at all segmental levels of the spinal cord project to the medial and lateral hypothalamus and several telencephalic regions (Bromm & Desmedt, 1995). These neurons are the link between tissue injury and the hypothalamic response in which hormonal messengers play a critical role.
The hypothalamic paraventricular nucleus (PVN) serve as the coordinating center for the hypothalamo-pituitary-adrenocortical (HPA) axis. Most of the hypothalamic and preoptic nuclei neurons projects to the PVN. Neurons from the PVN also, receives sensory input from the numerous reticular areas, including the ventrolateral medulla, dorsal raphe nucleus, nucleus raphe magnus, LC, dorsomedial nucleus, and the nucleus tractus solitarius (for review, see Sawchenko & Swanson 1982; Peschanski & Weil-Fugacza 1987; Lopez et al. 1991). Afferents from the hippocampus and amygdala also innervates the PVN.
When the PVN is input from the above areas, it initiate a complex series of events regulated by feedback mechanisms, which ready the organism for behaviors that will maximized its ability to deal with an immediate threat (see diagram 3)(Bromm & Desmedt 1995). This response is commonly referred to as "flight or fight". The PVN has been shown to induce these autonomic responses via both neural and hormonal pathways. Studies shows that it sends direct projections to the sympathetic intermediolateral cell column in the thoracolumbar spinal cord, and to the parasympathetic vagal complex, sources preganglionic autonomic outflow (for review, see Krukoff 1990). In addition, it signals the release of epinephrine and norepinephrine from the adrenal medulla. Thus, these networks of intercommunication implicate the involvement of the HPA axis in the neuroendocrinologic and autonomic manifestations of emotion during pain states.
In addition to controlling neuroendocrine and autonomic activity, the HPA axis is also involved in the coordination of emotional arousal with behavior (for review, see Panskepp 1986). Studies found that direct stimulation of the hypothalamus can elicit well-organized patterns of behavior, including defensive threat behaviors, accompanied by autonomic manifestations (for review, see Hess 1954; Mancia and Zanchetti 1981; Janig 1985a, b). Hence, suggesting that the hypothalamus played a major role in coordinating behaviors and bodily adjustments to challenging circumstance or appropriate biological stimuli. Furthermore, at high level of distress, stress hormones, especially glucocorticoids, may affect central emotional arousal, reducing startle thresholds and influencing cognition (for review, see Sapolsky 1992). A study done by Saphier in 1987 shows that cortisol alters the firing rate of neurons in the limbic forebrain (Bromm & Desmedt 1995). In sum, the HPA axis appears to have the primary responsibility for coordinating behavioral readiness with physiological capability, awareness, and cognitive function.
In summary, the emotional dimension of pain largely involves the combine effect from both the DBN and the HPA axis. This process begins with excitation of the central noradrenergic pathways associated with hypervigilance and fear (the LC and the DNB), as well as the spinothalamocortical pathways, in response to noxious stimuli. Thus leading to the integration of emotion with pain.
The HPA axis enhanced the arousal by activating the neuroendocrine and autonomic mechanisms. These mechanisms then evoke the necessary responses to prepare the organism for flight-or-fight behavior. Also adding to this is the stress-induce responses, which contributes to the pain states.