Spinal Pathways 1 Homework

Abstract

Central neuropathic pain following lesions within the CNS, such as spinal cord injury, is one of the most excruciating types of chronic pain and one of the most difficult to treat. The role of spinothalamic pathways in this type of pain is not clear. Previous studies suggested that spinothalamic tract lesions are necessary but not sufficient for development of central pain, since deficits of spinothalamic function were equally severe in spinal cord injured people with and without pain. The aim of the present study was to examine spinothalamic tract function by quantitative sensory testing before and after activation and sensitization of small diameter afferents by applying menthol, histamine or capsaicin to the distal skin areas where spontaneous pain was localized. Investigations were performed in matched groups each of 12 patients with and without central pain below the level of a clinically complete spinal cord injury, and in 12 able-bodied controls. To test peripheral C fibre function, axon reflex vasodilations induced by histamine and capsaicin applications were quantified. In eight patients with pain, sensations of the same quality as one of their major individual pain sensations were rekindled by heat stimuli in combination with topical capsaicin (n = 7) or by cold stimuli (n = 1). No sensations were evoked in pain-free patients (P < 0.01). Capsaicin-induced axon reflex vasodilations were significantly larger in pain patients with heat- and capsaicin-evoked sensations in comparison to pain patients without capsaicin-provoked sensations. These results suggest that intact thermosensitive nociceptive afferents within lesioned spinothalamic tract pathways distinguish people with central pain from those without. The ability to mimic chronic pain sensations by activation of thermosensory nociceptive neurons implies that ongoing activity in these residual spinothalamic pathways plays a crucial role in maintaining central pain. We propose that processes associated with degeneration of neighbouring axons within the tract, such as inflammation, may trigger spontaneous activity in residual intact neurons that act as a ‘central pain generator’ after spinal cord injury.

spinal cord injury, central neuropathic pain, spinothalamic tract, sensitization, nociceptive afferents

Introduction

Central pain that develops after lesions within the CNS, such as stroke, spinal cord injury (SCI) and multiple sclerosis, is one of the most excruciating and therapeutically refractory types of neuropathic pain (Finnerup et al., 2005; Siddall and Middleton, 2006). One reason for the lack of success in treating these types of pain is that the mechanisms underlying central pain are not fully understood.

A particularly puzzling question has been the role of the spinothalamic tract in central pain syndromes (Finnerup and Jensen, 2004). Multiple studies in central pain patients performed over the last two decades have demonstrated deficits of temperature and pain sensation within the painful area indicating that lesions of the spinothalamic projections are essential for development of pain (Beric et al., 1988; Boivie et al., 1989; Parrent et al., 1992; Vestergaard et al., 1995; Eide et al., 1996; Bowsher et al., 1998; Defrin et al., 2001; Finnerup et al., 2003; Finnerup and Jensen, 2004; Österberg et al., 2005; Ducreux et al., 2006; Finnerup et al., 2007a). However, as differences in altered sensitivity to thermal and nociceptive stimuli were not found in patients with pain compared to patients without pain after central lesions, it has been suggested that such lesions alone are not sufficient to generate central pain (Defrin et al., 2001; Finnerup et al., 2003; Finnerup and Jensen, 2004; Ducreux et al., 2006; Siddall and Middleton, 2006; Finnerup et al., 2007a). Thus, despite clear evidence for their relevance, the exact impact of lesions of the spinothalamic tract remains unclear.

About 30–40% of spinal cord injured people suffer from neuropathic pain due to lesions of nervous structures after SCI (Störmer et al., 1997; Siddall et al., 1999, 2003). In the taxonomy of the International Association for the Study of Pain (IASP), at-level pain, i.e. neuropathic pain related to the level of the injury, is distinguished from below-level pain localized distal from the site of injury (Siddall et al., 2000, 2002, 2003; Vierck et al., 2000). While at-level pain may be driven by both peripheral and central components, below-level pain is considered to be a central pain syndrome directly caused by the lesion to the spinal cord (Siddall et al., 2000; Finnerup and Jensen, 2004; Wasner et al., 2007). In terms of the underlying pathophysiology, it has been proposed that, after SCI, abnormal activity may arise as a result of a ‘spinal pain generator’ formed by neuronal hyperexcitability at the lesion site due to release of the excitatory amino acid glutamate, up-regulation of sodium channels, activation of glial cells during inflammatory processes triggered by the lesion and loss of intraspinal and descending inhibitory pathways (Vierck et al., 2000; Finnerup and Jensen, 2004; Yezierski, 2005; Waxman and Hains, 2006). This is in accord with a recent patient study indicating that neuronal hyperexcitability in the spinal cord is a key element in central neuropathic pain, whereas loss of spinothalamic function does not appear to be a pain predictor (Finnerup et al., 2007b). As preserved neuronal function is essential for development of hyperexcitability, the question arises as to whether residual intact spinothalamic tract neurons can be identified in subjects with central pain following SCI.

In the present study, spinothalamic tract function was tested quantitatively in people with and without below-level pain following clinically complete SCI by quantitative sensory testing before and after activation and sensitization of small diameter afferents by applying menthol, histamine or capsaicin to the distal skin areas where spontaneous pain was localized. The responses to these three chemicals can be used to activate specific spinothalamic tract pathways. We reasoned that stimulation after sensitization of small fibre peripheral afferents including nociceptors and thermal afferents in a below-level area with severe sensory deficits might generate sensations that were missed by conventional quantitative sensory testing (Wasner et al., 2007). This would imply the existence of persisting connections between the periphery and the central pathways.

Materials and Methods

Subjects

The function of the spinothalamic tract was tested in three groups each of 12 age- and sex-matched subjects: (i) SCI people with central neuropathic pain below the spinal lesion, (ii) SCI people without any pain below the lesion and (iii) able-bodied pain-free control subjects (Tables 1–3).

SCI subjects were included according to the following criteria. To ensure a central lesion affecting the spinal cord above the conus medullaris, we required (i) that the traumatic SCI was not lower than the 10th thoracic vertebra and (ii) at least one clinical sign at or proximal to the neurological level of the test area indicated a central lesion (e.g. brisk Achilles jerks when testing the lower leg). Patients had to be classified as having a complete spinal cord lesion according to the American Spinal Injury Association's standards for classification of SCI (ASIA, grade A, see later). In cases in which patients had a zone of partial preservation (ZPP, see later), this needed to be well localized outside the test area.

Neuropathic pain was defined as chronic pain in an area of sensory abnormalities developed after SCI. The definition of below-level pain was that the painful area was at least two dermatome segments below the lesion level to ensure that the pain was localized below the neurological level (Finnerup et al., 2003) (Table 1). The pain needed not to have any primary relation to spasm or any other movement.

Table 1.

Clinical characteristics of spinal cord injured people with central pain below the level of injury

No Age/Sex Neurological level ASIA Time since injury (months) Mechanism of injury Area of below-level pain Test area At-level pain Pain medication Syrinx 
22/M T4 Water skiing accident Upper legs, feet Feet – – – 
33/M T4 A, ZPP (T7) 95 Bike accident Legs Left lower leg Yes – C6–T5 
25/M T1 A, ZPP (T4) 28 Motor vehicle accident Lower abdomen, right knee Left lower abdomen Yes – – 
52/M T5 348 Motor vehicle accident Legs Left upper leg – – C7–T2 
46/M T5 322 Motor vehicle accident Legs Left lower leg and foot Yes – – 
34/M C7 A, ZPP (T4) 42 Diving accident Left lower leg Left lower leg – Gabapentin, amitriptyline – 
40/M T10 44 Motor vehicle accident Legs Right lower leg and both feet – Gabapentin, amitriptyline – 
61/F T10 34 Fall from height Legs Right lower leg Yes Gabapentin – 
29/M C7 53 Motor vehicle accident Feet Left lower leg and foot – Gabapentin, oxycodone, amitriptyline – 
10 61/M T10 48 Motor vehicle accident Upper legs Right upper leg – Pregabalin – 
11 57/M T7 384 Motor vehicle accident Feet and left lower leg Feet – – – 
12 29/M T4 34 Motor vehicle accident Feet Left foot Yes Pregabalin, amitriptyline – 
No Age/Sex Neurological level ASIA Time since injury (months) Mechanism of injury Area of below-level pain Test area At-level pain Pain medication Syrinx 
22/M T4 Water skiing accident Upper legs, feet Feet – – – 
33/M T4 A, ZPP (T7) 95 Bike accident Legs Left lower leg Yes – C6–T5 
25/M T1 A, ZPP (T4) 28 Motor vehicle accident Lower abdomen, right knee Left lower abdomen Yes – – 
52/M T5 348 Motor vehicle accident Legs Left upper leg – – C7–T2 
46/M T5 322 Motor vehicle accident Legs Left lower leg and foot Yes – – 
34/M C7 A, ZPP (T4) 42 Diving accident Left lower leg Left lower leg – Gabapentin, amitriptyline – 
40/M T10 44 Motor vehicle accident Legs Right lower leg and both feet – Gabapentin, amitriptyline – 
61/F T10 34 Fall from height Legs Right lower leg Yes Gabapentin – 
29/M C7 53 Motor vehicle accident Feet Left lower leg and foot – Gabapentin, oxycodone, amitriptyline – 
10 61/M T10 48 Motor vehicle accident Upper legs Right upper leg – Pregabalin – 
11 57/M T7 384 Motor vehicle accident Feet and left lower leg Feet – – – 
12 29/M T4 34 Motor vehicle accident Feet Left foot Yes Pregabalin, amitriptyline – 

View Large

SCI pain-free control subjects should not have had any sensation and particularly not pain (including any spasm- or movement-related pain) below the neurological level since the time of the injury (Table 2).

Table 2

Clinical characteristics of spinal cord injured people without pain below the level of injury

No. Age/Sex Neurological level ASIA Time since injury (months) Mechanism of injury At-level pain Syrinx 
39/M T5 72 Motor vehicle accident Yes – 
22/M T4 12 Motor vehicle accident – – 
45/M T4 39 Motor vehicle accident Yes T2–T3 
61/M T4 450 Motor vehicle accident – – 
35/M C6 20 Diving accident Yes – 
38/M T5 A, ZPP (T8) 18 Spinal infarction – – 
36/M T9 226 Motor vehicle accident – T6–T9 
60/M C4 A, ZPP (C7) 502 Motor vehicle accident – – 
30/M T7 A, ZPP (L2) 50 Motor vehicle accident – – 
10 67/M T10 93 Fall from height – – 
11 44/M T7 327 Motor vehicle accident – – 
12 46/M T8 215 Motor vehicle accident – – 
No. Age/Sex Neurological level ASIA Time since injury (months) Mechanism of injury At-level pain Syrinx 
39/M T5 72 Motor vehicle accident Yes – 
22/M T4 12 Motor vehicle accident – – 
45/M T4 39 Motor vehicle accident Yes T2–T3 
61/M T4 450 Motor vehicle accident – – 
35/M C6 20 Diving accident Yes – 
38/M T5 A, ZPP (T8) 18 Spinal infarction – – 
36/M T9 226 Motor vehicle accident – T6–T9 
60/M C4 A, ZPP (C7) 502 Motor vehicle accident – – 
30/M T7 A, ZPP (L2) 50 Motor vehicle accident – – 
10 67/M T10 93 Fall from height – – 
11 44/M T7 327 Motor vehicle accident – – 
12 46/M T8 215 Motor vehicle accident – – 

View Large

Able-bodied control subjects had to be free of any chronic or acute pain, any medication and any neurological disorder.

Фонтейн заплатил за этого бегемота дешифровки два миллиарда и хотел, чтобы эти деньги окупились сполна. Каждая минута простоя ТРАНСТЕКСТА означала доллары, спущенные в канализацию. - Но, Мидж… - сказал Бринкерхофф.  - ТРАНСТЕКСТ не устраивает перерывов.

Он трудится день и ночь.

0 comments

Leave a Reply

Your email address will not be published. Required fields are marked *